The establishment of pregnancy is a complex process that requires a well-coordinated interaction between the implanting conceptus and the maternal uterus. In pigs, the conceptus undergoes dramatic morphological and fu...The establishment of pregnancy is a complex process that requires a well-coordinated interaction between the implanting conceptus and the maternal uterus. In pigs, the conceptus undergoes dramatic morphological and functional changes at the time of implantation and introduces various factors, including estrogens and cytokines,interleukin-1β2(IL1 B2), interferon-γ(IFNG), and IFN-δ(IFND), into the uterine lumen. In response to ovarian steroid hormones and conceptus-derived factors, the uterine endometrium becomes receptive to the implanting conceptus by changing its expression of cell adhesion molecules, secretory activity, and immune response. Conceptus-derived estrogens act as a signal for maternal recognition of pregnancy by changing the direction of prostaglandin(PG) F2αfrom the uterine vasculature to the uterine lumen. Estrogens also induce the expression of many endometrial genes,including genes related to growth factors, the synthesis and transport of PGs, and immunity. IL1 B2, a pro-inflammatory cytokine, is produced by the elongating conceptus. The direct effect of IL1 B2 on endometrial function is not fully understood. IL1 B activates the expression of endometrial genes, including the genes involved in IL1 B signaling and PG synthesis and transport. In addition, estrogen or IL1 B stimulates endometrial expression of IFN signaling molecules,suggesting that estrogen and IL1 B act cooperatively in priming the endometrial function of conceptus-produced IFNG and IFND that, in turn, modulate endometrial immune response during early pregnancy. This review addresses information about maternal-conceptus interactions with respect to endometrial gene expression in response to conceptus-derived factors, focusing on the roles of estrogen and IL1 B during early pregnancy in pigs.展开更多
Injury of the periodontium followed by inflammatory response often leads to root resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact...Injury of the periodontium followed by inflammatory response often leads to root resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts.Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin(IL)-1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin.The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts(p HCB) was compared with a human cementoblast cell line(HCEM). The p HCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand(RANKL) and osteoprotegerin(OPG). In a co-culture system consisting of osteoclast precursors(blood monocytes) and p HCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors(IL1-R1 and IL1-R2). Treatment with IL-1β potently upregulated RANKL expression but not of OPG. p HCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the p HCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth.展开更多
AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus kerati...AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin(mT OR)/Toll-like receptor 4(TLR4) signaling pathway.METHODS:Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction(PCR).RESULTS:In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION:Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.展开更多
BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α)...BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.展开更多
Dear Editor,Galectin-1, one of galactoside-binding lectin family proteins, has been shown to regulate cell growth, migration, and proliferation, where it binds many receptors depending on their glycosylation profile, ...Dear Editor,Galectin-1, one of galactoside-binding lectin family proteins, has been shown to regulate cell growth, migration, and proliferation, where it binds many receptors depending on their glycosylation profile, rather than its specific receptors.展开更多
Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic ...Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL-1β, 20ng/ml TNF-1α and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4 h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expres- ion of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32 P- end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cul- tured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cul- tured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-1β, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2. 3-fold and 1. 6-fold, respectively). ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9- fold, 1.7-fold and 1.1-fold, respectively). The results suggest that calf aortic SMCs could ex- press MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP-1 mRNA and protein, and the former is more effective than the latter.展开更多
AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experime...AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy donors.PBMCs were activated by lipopolysaccharide(LPS) stimulation before being treated with Adenosine triphosphate(ATP,1 mmol/L),human α-defensin-5(HD-5,50 μg/mL),and/or nigericin(Nig,30 μmol/L).For each experiment,the culture supernatants were collected separately from the cells.Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies.RESULTS:We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation.In the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely inhibited.Similarly,in the presence of HD-5,the release of IL-1β,but not the processing of IL-1β,was significantly inhibited from LPS-activated monocytes stimulated with Nig.Finally,we treated LPS-activated monocytes with ATP and Nig and collected the supernatants.We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes.Interestingly,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by HD-5.All images are representative of three independent experiments.CONCLUSION:These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.展开更多
The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulati...The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulation output; voltage intensity, 1 to 4 V; frequency, 1 Hz) was applied to bilateral equvalent Quchi (LI 11 ) acupoints for 30 min. Intraperitoneal injection of LPS (0111: B 4) at a single dose of 100 μg/kg caused high rectal temperature in rats, which was remarably sup pressed by EA either given simultaneously or 2 h after LPS injection. No difference in reduction of fever was found between two groups of rats treated by EA at different times. The rats that received adIninistration of hrIL-1β(2ng) or PGE2(3μg) into the prooptic area (POA) developed the acute and high fevers. The temperature in both cases was significantly decreased after EA stimulation. EA also partially inhibited the fever caused by intravenous injection of 0. 5μg/kg IL-1β. The they temperature increased within 1℃ in the rats that got intravenous injection of PGE2 (1. 5mg/kg), and EA did not present strong inhibitory effect on it. The present results demonstrate that EA possesses an antipyretic effect in rats and suggest that which may attribute to the suppression of the actions of IL-1β and/or PGE2 in the development of fever.展开更多
Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the producti...Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β(IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold(PWT) and paw withdrawal latency(PWL) were significantly decreased after spinal nerve ligation(SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mR NA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mR NA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.展开更多
AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitam...AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitamin D receptor(VDR) siR NA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3(1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR si RNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and m RNA expression, respectively. Atg16L1 si RNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mR NA expression.RESULTS The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mR NA expression, membranous Atg16L1 protein expression leading to autophagic LC3 II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR si RNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.CONCLUSION Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.展开更多
The protective effect of niacinamide on interleukin-1β (IL-1β)-induced annulus fibrosus (AF) type Ⅱ collagen degeneration in vitro and the mechanism were investigated. Chiba's interverte-bral disc (IVD) culture...The protective effect of niacinamide on interleukin-1β (IL-1β)-induced annulus fibrosus (AF) type Ⅱ collagen degeneration in vitro and the mechanism were investigated. Chiba's interverte-bral disc (IVD) culture models in rabbits were established and 48 IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups: normal control group, niacinamide-treated group, type Ⅱ collagen degneration group (IL-1β) and treatment group (niacinamide+IL-1β). After culture for one week, AFs were collected for inducible nitric oxide synthase (iNOS), cysteine containing aspar-tate specific protease-3 (Caspase-3) and type Ⅱ collagen immunohistochemical examination, and type Ⅱ collagen reverse transcription polymerase chain reaction (RT-PCR). The results showed that rate of iNOS positive staining AF cells in the 4 groups was 17.6%, 10.9%, 73.9% and 19.3% respec-tively. The positive rate in treatment group was significantly lower than in the type Ⅱ collagen de-generation group (P<0.01). Rate of Caspase-3 positive staining AF cells in the 4 groups was 3.4%, 4.2%, 17.6% and 10.3% respectively. The positive rate in treatment group was lower than in the type Ⅱ collagen degeneration group (P<0.01). Type Ⅱ collagen staining demonstrated that lamellar structure and continuity of collagen in treatment group was better reversed than in the degeneration group. RT-PCR revealed that the expression of type Ⅱ collagen in treatment group was significantly stronger than that in type Ⅱ collagen degeneration group (P<0.01). It was concluded that niacina-mide could effectively inhibit IL-1β stimulated increase of iNOS and Caspase-3 in AF, and alleviate IL-1β-caused destruction and synthesis inhibition of type Ⅱ collagen. Niacinamide is of potential for clinical treatment of IVD degeneration.展开更多
Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little i...Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little is known regarding the influence of the signalling from bone. Additionally, the collagenases and stromelysin-1 are involved in cartilage catabolism through mitogen-activated protein kinase(MAPK) signalling, but the role of the gelatinases has not been elucidated. Here, we studied the influence of osteoclastic signals on chondrocytes by characterising the expression of interleukin-1β(IL-1β)-induced gelatinases through MAPK signalling. We found that osteoclast-conditioned media attenuated the gelatinase activity in chondrocytes. However, IL-1β induced increased levels of gelatinase activity in the conditioned media group relative to the mono-cultured chondrocyte group. More specifically, IL-1β restored high levels of gelatinase activity in c-Jun N-terminal kinase inhibitor-pretreated chondrocytes in the conditioned media group and led to lower levels of gelatinase activity in extracellular signal-regulated kinase or p38 inhibitor-pretreated chondrocytes. Gene expression generally correlated with protein expression. Taken together, these results show for the first time that signals from osteoclasts can influence gelatinase activity in chondrocytes. Furthermore, these data show that IL-1β restores gelatinase activity through MAPK inhibitors; this information can help to increase the understanding of the gelatinase modulation in articular cartilage.展开更多
Objective To elucidate the effect of interleukin-1β (IL-1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly establis...Objective To elucidate the effect of interleukin-1β (IL-1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Luc1 plasmid which contained hGH gene promoter -484 to +30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 103 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5’-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 μmol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μmol/L) completely blocked the stimulatory effect of IL-1β, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1β. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected induction of hGH promoter activity by IL-1β. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the -196 to -132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the –196 to –132 bp of the gene, but it may be unlinked with Pit-1 protein.展开更多
Objective To investigate the effect of interleukin-6 (IL-6) on the apoptosis of annulus fibrosus (AF) cell induced by interleukin-1β (IL-1β). Methods Cultured AF cells were divided into 6 groups and treated with no ...Objective To investigate the effect of interleukin-6 (IL-6) on the apoptosis of annulus fibrosus (AF) cell induced by interleukin-1β (IL-1β). Methods Cultured AF cells were divided into 6 groups and treated with no drug, 10 ng/mL IL-6,10 ng/mL IL-1β,10 ng/mL IL-1β and Z-VAD-FMK (a caspase-9 inhibitor),10 ng/mL IL-1β and 10 ng/mL IL-6,10 ng/mL IL-1β and 100 ng/mL IL-6, respectively. After three days of culture, the apoptosis rate, the positive rates of caspase-3, -8, and -9 of AF cells were detected with flow cytometry. Results The apoptosis rates of cells in group 1 to 6 were 2.67%±1.08%, 2.71%±0.53%, 20.37%±1.57%, 11.34%±0.67%, 18.17%±0.74%, and 9.42%±1.08%, respectively. There was no significant difference between group 1 and 2, while the apoptosis rates of group 4, 5, and 6 were significantly lower than group 3 (P=0.001,P=0.172, and P=0.001, respectively). Positive rates of caspase-3 in group 5 (12.35%±0.64%) and 6 (9.26%±0.36%) were significantly lower than group 3 (17.14%±0.72%; P=0.001 and P<0.001, respectively). And positive rates of caspase-9 in group 5 (15.13%±1.45%) and 6 (10.17%±2.50%) were significantly lower than group 3 (19.4%±0.98%; P=0.014 and P=0.004, respectively). But there was not obvious change of caspase-8 activity after IL-6 was added. Conclusion IL-6 is capable of protecting AF cells from IL-1β induced apoptosis in vitro. Mechanism of the protection is related with the inhibition of caspase-3 and -9 activities.展开更多
Background: Interleukin-1β(IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cereb...Background: Interleukin-1β(IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid(CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide(LPS)-induced inflammation.Methods: Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient(QAlb) was used.Expression of IL-1β(Il1B) and its receptor type Ⅰ(Il1r1) and type Ⅱ(Il1r2) and matrix metalloproteinase(Mmp) 3 and 9 was evaluated in the choroid plexus(CP).Results: Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, respectively.Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected m RNA expression of Il1B, Il1r1 and Il1r2 in the CP. The m RNA expression of Mmp3 and Mmp9 was not detected.Conclusions: The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.展开更多
Objective To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischem...Objective To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phos-phorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1βmRNA level was measured by ribonuclease protection assay. Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1βmRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO. Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1βmRNA via the inhibition of ERK pathway.展开更多
AIM:To examine the effect of interleukin-l-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist(IL-1RN) polymorphism among the patients with chronichepatitis B virus (HBV) infection (HCC and non-HCC).METHO...AIM:To examine the effect of interleukin-l-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist(IL-1RN) polymorphism among the patients with chronichepatitis B virus (HBV) infection (HCC and non-HCC).METHODS:Genomic DNA from 136 Thai patients withchronic HBV infection (HCC=46 and non-HCC=90) and152 healthy individuals was genotyped for IL-1β genepolymorphism (-511) using polymerase chain reactionwith sequence specific primers (PCR-SSP).The variablenumber of tandem repeats (VNTR) of IL-1RN gene wasassessed by a PCR-based assay.The association betweenthese genes and status of the disease was evaluated byX^2 test.RESULTS:IL-1B-511 genotype C/C was found tobe significantly different in patients with HCC whencompared with healthy individuals (P=0.036,OR=2.29,95%CI=1.05-4.97) and patients without HCC (P=0.036,OR=2.52,95%CI=1.05-6.04).Analysis of allelefrequencies of IL-1B-511 showed that IL-1B-511 Callele was also significantly increased in patients withHCC,compared to that in healthy control (P=0.033,OR=1.72,95%CI=1.04-2.84).However,no significantassociation in IL-1RN gene was found between the twogroups.CONCLUSION:IL-1B-511C allele,which may beassociated with high IL-1B production in the liver,is agenetic marker for the development of HCC in chronic hepatitis B patients in Thai population.展开更多
AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were random...AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane.Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 (P＜0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and (P＜0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20) μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07) μg/L (P＜0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P＜0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred.CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.展开更多
Protective effect of interleukin 1β (IL 1β) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After...Protective effect of interleukin 1β (IL 1β) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 μl 1 ng/ml IL 1β and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal α motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too ( P< 0 01). These results suggest that exogenous IL 1β protects α motor neurons from degeneration and necrosis after peripheral nerve injury.展开更多
基金Support for the work from the authors’laboratory described in this review paper has been provided by the Bio Green 21 Program(20050603050120070301034040+8 种基金 20080401034003 PJ007997 PJ009610 PJ01110301PJ01119103)the Rural Development Administrationa National Research Foundation grant funded by the Korean Government(KRF-2005-003-F00017,KRF-2007-521-F00030,NRF-2010-0012304,NRF-2010-10012304 NRF-2012R1A2A2A01047079 NRF-2015R1D1A1A01058356,Republic of Korea
文摘The establishment of pregnancy is a complex process that requires a well-coordinated interaction between the implanting conceptus and the maternal uterus. In pigs, the conceptus undergoes dramatic morphological and functional changes at the time of implantation and introduces various factors, including estrogens and cytokines,interleukin-1β2(IL1 B2), interferon-γ(IFNG), and IFN-δ(IFND), into the uterine lumen. In response to ovarian steroid hormones and conceptus-derived factors, the uterine endometrium becomes receptive to the implanting conceptus by changing its expression of cell adhesion molecules, secretory activity, and immune response. Conceptus-derived estrogens act as a signal for maternal recognition of pregnancy by changing the direction of prostaglandin(PG) F2αfrom the uterine vasculature to the uterine lumen. Estrogens also induce the expression of many endometrial genes,including genes related to growth factors, the synthesis and transport of PGs, and immunity. IL1 B2, a pro-inflammatory cytokine, is produced by the elongating conceptus. The direct effect of IL1 B2 on endometrial function is not fully understood. IL1 B activates the expression of endometrial genes, including the genes involved in IL1 B signaling and PG synthesis and transport. In addition, estrogen or IL1 B stimulates endometrial expression of IFN signaling molecules,suggesting that estrogen and IL1 B act cooperatively in priming the endometrial function of conceptus-produced IFNG and IFND that, in turn, modulate endometrial immune response during early pregnancy. This review addresses information about maternal-conceptus interactions with respect to endometrial gene expression in response to conceptus-derived factors, focusing on the roles of estrogen and IL1 B during early pregnancy in pigs.
基金Ratchadaphiseksomphot Endowment Fund Chulalongkorn University(R/F_2557_021_03_32)Integrated-Innovation Academic Center’Chulalongkorn University Centenary Academic Development Project+1 种基金The 2012 Research Chair GrantThailand National Science and Technology Development Agency(NSTDA)
文摘Injury of the periodontium followed by inflammatory response often leads to root resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts.Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin(IL)-1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin.The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts(p HCB) was compared with a human cementoblast cell line(HCEM). The p HCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand(RANKL) and osteoprotegerin(OPG). In a co-culture system consisting of osteoclast precursors(blood monocytes) and p HCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors(IL1-R1 and IL1-R2). Treatment with IL-1β potently upregulated RANKL expression but not of OPG. p HCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the p HCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth.
基金Supported by the National Natural Science Foundation of China(No.81470609No.81500695)
文摘AIM:To elucidate the effect of rapamycin on regulating the production of interleukin(IL)-1β in Aspergillus fumigatus(A.fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A.fumigatus keratitis is associated with the mammalian target of rapamycin(mT OR)/Toll-like receptor 4(TLR4) signaling pathway.METHODS:Fungal keratitis mouse models of susceptible C57 BL/6 mice were established using A.fumigatus.The mice were subsequently treated with rapamycin.The protein levels of p-mT OR,TLR4,and IL-1β in normal and infected corneal tissue were measured by Western blot.The TLR4 and IL-1β m RNA levels were determined by real-time polymerase chain reaction(PCR).RESULTS:In C57 BL/6 mice,rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine,IL-1β.The expression of TLR4,stimulated by A.fumigatus,was reduced as well when the mT OR signaling pathway was suppressed by rapamycin.CONCLUSION:Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β.The inhibitory effect on IL-1β expression can be associated with the mT OR/TLR4 signaling pathway in A.fumigatus infection in mice.
文摘BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.
基金Supported by Bayer Yakuhin Ltd,the Uehara Memorial Foundation,the Eye Research Foundation for the Aged,and the Japan National Society for the Prevention of Blindness
文摘Dear Editor,Galectin-1, one of galactoside-binding lectin family proteins, has been shown to regulate cell growth, migration, and proliferation, where it binds many receptors depending on their glycosylation profile, rather than its specific receptors.
基金This project was supported by a grant from National Natural Science Foundation of China !(No. 39470289).
文摘Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL-1β, 20ng/ml TNF-1α and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4 h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expres- ion of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32 P- end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cul- tured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cul- tured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-1β, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2. 3-fold and 1. 6-fold, respectively). ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9- fold, 1.7-fold and 1.1-fold, respectively). The results suggest that calf aortic SMCs could ex- press MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP-1 mRNA and protein, and the former is more effective than the latter.
基金Supported by NIH R21 AI085416 (to Shi J)NIH NCRR P20-RR017686 (to PI:Daniel MarcusShi J)
文摘AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy donors.PBMCs were activated by lipopolysaccharide(LPS) stimulation before being treated with Adenosine triphosphate(ATP,1 mmol/L),human α-defensin-5(HD-5,50 μg/mL),and/or nigericin(Nig,30 μmol/L).For each experiment,the culture supernatants were collected separately from the cells.Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies.RESULTS:We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation.In the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely inhibited.Similarly,in the presence of HD-5,the release of IL-1β,but not the processing of IL-1β,was significantly inhibited from LPS-activated monocytes stimulated with Nig.Finally,we treated LPS-activated monocytes with ATP and Nig and collected the supernatants.We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes.Interestingly,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by HD-5.All images are representative of three independent experiments.CONCLUSION:These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.
文摘The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulation output; voltage intensity, 1 to 4 V; frequency, 1 Hz) was applied to bilateral equvalent Quchi (LI 11 ) acupoints for 30 min. Intraperitoneal injection of LPS (0111: B 4) at a single dose of 100 μg/kg caused high rectal temperature in rats, which was remarably sup pressed by EA either given simultaneously or 2 h after LPS injection. No difference in reduction of fever was found between two groups of rats treated by EA at different times. The rats that received adIninistration of hrIL-1β(2ng) or PGE2(3μg) into the prooptic area (POA) developed the acute and high fevers. The temperature in both cases was significantly decreased after EA stimulation. EA also partially inhibited the fever caused by intravenous injection of 0. 5μg/kg IL-1β. The they temperature increased within 1℃ in the rats that got intravenous injection of PGE2 (1. 5mg/kg), and EA did not present strong inhibitory effect on it. The present results demonstrate that EA possesses an antipyretic effect in rats and suggest that which may attribute to the suppression of the actions of IL-1β and/or PGE2 in the development of fever.
基金supported by grants from the National Natural Science Foundation of China(Nos.31100801 and81200858)
文摘Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β(IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold(PWT) and paw withdrawal latency(PWL) were significantly decreased after spinal nerve ligation(SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mR NA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mR NA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.
基金Supported by the Ministry of Science and Technology[MOST 103-2314-B-182-032(in part)]the Chang Gung Memorial Hospital,No.CMRPG8B1431,No.CMRPG8B1481 and No.CMRPG880443the Stem Cell Research Core Laboratory (grant CLRPG8B0052) for technical support
文摘AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitamin D receptor(VDR) siR NA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3(1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR si RNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and m RNA expression, respectively. Atg16L1 si RNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mR NA expression.RESULTS The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mR NA expression, membranous Atg16L1 protein expression leading to autophagic LC3 II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR si RNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.CONCLUSION Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.
文摘The protective effect of niacinamide on interleukin-1β (IL-1β)-induced annulus fibrosus (AF) type Ⅱ collagen degeneration in vitro and the mechanism were investigated. Chiba's interverte-bral disc (IVD) culture models in rabbits were established and 48 IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups: normal control group, niacinamide-treated group, type Ⅱ collagen degneration group (IL-1β) and treatment group (niacinamide+IL-1β). After culture for one week, AFs were collected for inducible nitric oxide synthase (iNOS), cysteine containing aspar-tate specific protease-3 (Caspase-3) and type Ⅱ collagen immunohistochemical examination, and type Ⅱ collagen reverse transcription polymerase chain reaction (RT-PCR). The results showed that rate of iNOS positive staining AF cells in the 4 groups was 17.6%, 10.9%, 73.9% and 19.3% respec-tively. The positive rate in treatment group was significantly lower than in the type Ⅱ collagen de-generation group (P<0.01). Rate of Caspase-3 positive staining AF cells in the 4 groups was 3.4%, 4.2%, 17.6% and 10.3% respectively. The positive rate in treatment group was lower than in the type Ⅱ collagen degeneration group (P<0.01). Type Ⅱ collagen staining demonstrated that lamellar structure and continuity of collagen in treatment group was better reversed than in the degeneration group. RT-PCR revealed that the expression of type Ⅱ collagen in treatment group was significantly stronger than that in type Ⅱ collagen degeneration group (P<0.01). It was concluded that niacina-mide could effectively inhibit IL-1β stimulated increase of iNOS and Caspase-3 in AF, and alleviate IL-1β-caused destruction and synthesis inhibition of type Ⅱ collagen. Niacinamide is of potential for clinical treatment of IVD degeneration.
基金funded by National Natural Science Foundation of China (81201211, 81471803)Funding of State Key Laboratory of Oral Diseases (SKLOD201527)The youth start-up fund (2015SCU11013)
文摘Osteoarthritis is recognised to be an interactive pathological process involving the cartilage, subchondral bone and synovium. The signals from the synovium play an important role in cartilage metabolism, but little is known regarding the influence of the signalling from bone. Additionally, the collagenases and stromelysin-1 are involved in cartilage catabolism through mitogen-activated protein kinase(MAPK) signalling, but the role of the gelatinases has not been elucidated. Here, we studied the influence of osteoclastic signals on chondrocytes by characterising the expression of interleukin-1β(IL-1β)-induced gelatinases through MAPK signalling. We found that osteoclast-conditioned media attenuated the gelatinase activity in chondrocytes. However, IL-1β induced increased levels of gelatinase activity in the conditioned media group relative to the mono-cultured chondrocyte group. More specifically, IL-1β restored high levels of gelatinase activity in c-Jun N-terminal kinase inhibitor-pretreated chondrocytes in the conditioned media group and led to lower levels of gelatinase activity in extracellular signal-regulated kinase or p38 inhibitor-pretreated chondrocytes. Gene expression generally correlated with protein expression. Taken together, these results show for the first time that signals from osteoclasts can influence gelatinase activity in chondrocytes. Furthermore, these data show that IL-1β restores gelatinase activity through MAPK inhibitors; this information can help to increase the understanding of the gelatinase modulation in articular cartilage.
文摘Objective To elucidate the effect of interleukin-1β (IL-1β) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Luc1 plasmid which contained hGH gene promoter -484 to +30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 103 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5’-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 μmol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μmol/L) completely blocked the stimulatory effect of IL-1β, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1β. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected induction of hGH promoter activity by IL-1β. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the -196 to -132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the –196 to –132 bp of the gene, but it may be unlinked with Pit-1 protein.
基金Supported by a grant from National Sciences Foundation of HubeiProvince (2004ABA193).
文摘Objective To investigate the effect of interleukin-6 (IL-6) on the apoptosis of annulus fibrosus (AF) cell induced by interleukin-1β (IL-1β). Methods Cultured AF cells were divided into 6 groups and treated with no drug, 10 ng/mL IL-6,10 ng/mL IL-1β,10 ng/mL IL-1β and Z-VAD-FMK (a caspase-9 inhibitor),10 ng/mL IL-1β and 10 ng/mL IL-6,10 ng/mL IL-1β and 100 ng/mL IL-6, respectively. After three days of culture, the apoptosis rate, the positive rates of caspase-3, -8, and -9 of AF cells were detected with flow cytometry. Results The apoptosis rates of cells in group 1 to 6 were 2.67%±1.08%, 2.71%±0.53%, 20.37%±1.57%, 11.34%±0.67%, 18.17%±0.74%, and 9.42%±1.08%, respectively. There was no significant difference between group 1 and 2, while the apoptosis rates of group 4, 5, and 6 were significantly lower than group 3 (P=0.001,P=0.172, and P=0.001, respectively). Positive rates of caspase-3 in group 5 (12.35%±0.64%) and 6 (9.26%±0.36%) were significantly lower than group 3 (17.14%±0.72%; P=0.001 and P<0.001, respectively). And positive rates of caspase-9 in group 5 (15.13%±1.45%) and 6 (10.17%±2.50%) were significantly lower than group 3 (19.4%±0.98%; P=0.014 and P=0.004, respectively). But there was not obvious change of caspase-8 activity after IL-6 was added. Conclusion IL-6 is capable of protecting AF cells from IL-1β induced apoptosis in vitro. Mechanism of the protection is related with the inhibition of caspase-3 and -9 activities.
基金supported by a project funded by the National Science Centre allocated on the basis of decision-DEC 2011/03/B/NZ9/00118supported by Ministry of Science and High Education
文摘Background: Interleukin-1β(IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid(CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide(LPS)-induced inflammation.Methods: Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient(QAlb) was used.Expression of IL-1β(Il1B) and its receptor type Ⅰ(Il1r1) and type Ⅱ(Il1r2) and matrix metalloproteinase(Mmp) 3 and 9 was evaluated in the choroid plexus(CP).Results: Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, respectively.Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected m RNA expression of Il1B, Il1r1 and Il1r2 in the CP. The m RNA expression of Mmp3 and Mmp9 was not detected.Conclusions: The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.
文摘Objective To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phos-phorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1βmRNA level was measured by ribonuclease protection assay. Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1βmRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO. Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1βmRNA via the inhibition of ERK pathway.
基金Supported by the Thailand Research Fund,RSA4680021
文摘AIM:To examine the effect of interleukin-l-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist(IL-1RN) polymorphism among the patients with chronichepatitis B virus (HBV) infection (HCC and non-HCC).METHODS:Genomic DNA from 136 Thai patients withchronic HBV infection (HCC=46 and non-HCC=90) and152 healthy individuals was genotyped for IL-1β genepolymorphism (-511) using polymerase chain reactionwith sequence specific primers (PCR-SSP).The variablenumber of tandem repeats (VNTR) of IL-1RN gene wasassessed by a PCR-based assay.The association betweenthese genes and status of the disease was evaluated byX^2 test.RESULTS:IL-1B-511 genotype C/C was found tobe significantly different in patients with HCC whencompared with healthy individuals (P=0.036,OR=2.29,95%CI=1.05-4.97) and patients without HCC (P=0.036,OR=2.52,95%CI=1.05-6.04).Analysis of allelefrequencies of IL-1B-511 showed that IL-1B-511 Callele was also significantly increased in patients withHCC,compared to that in healthy control (P=0.033,OR=1.72,95%CI=1.04-2.84).However,no significantassociation in IL-1RN gene was found between the twogroups.CONCLUSION:IL-1B-511C allele,which may beassociated with high IL-1B production in the liver,is agenetic marker for the development of HCC in chronic hepatitis B patients in Thai population.
基金Supported by the Traditional Chinese Medicine Administration Bureau Foundation of Jiangsu Province,No.9965the Applied Basic Research Program of Science and Technology Commission Foundation of Jiangsu Province,No.BJ2000327
文摘AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane.Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 (P＜0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and (P＜0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20) μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07) μg/L (P＜0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P＜0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred.CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.
文摘Protective effect of interleukin 1β (IL 1β) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 μl 1 ng/ml IL 1β and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal α motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too ( P< 0 01). These results suggest that exogenous IL 1β protects α motor neurons from degeneration and necrosis after peripheral nerve injury.
