Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer deve...Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer development and progression.Interleukin-8(IL-8)is overexpressed in gastric mucosa exposed to H.pylori.The expression of IL-8 directly correlates with a poor prognosis in gastric cancer.IL-8 is multifunctional.In addition to its potent chemotactic activity,it can induce proliferation and migration of cancer cells.In this review,we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer.The relationship between IL-8 and H.pylori is discussed.We also summarize the current therapeutics against IL-8 in gastric cancer.展开更多
AIM:To investigate the interaction between Xiaotan Sanjie(XTSJ) decoction and interleukin-8(IL-8) and its effect on adhesion,migration and invasion of SGC-7901 gastric cancer cells.METHODS:SGC-7901 gastric cancer cell...AIM:To investigate the interaction between Xiaotan Sanjie(XTSJ) decoction and interleukin-8(IL-8) and its effect on adhesion,migration and invasion of SGC-7901 gastric cancer cells.METHODS:SGC-7901 gastric cancer cells were exposed to serum containing XTSJ decoction and/orIL-8(1 ng/m L).SGC-7901 cell adhesion to fibronectin,an extracellular matrix component,was detected using the Cell Counting Kit-8.Migration and invasion abilities of SGC-7901 cells were detected by scratch wound and Transwell chamber assays.Then,protein(immunofluorescence and Western blot) and m RNA levels(quantitative polymerase chain reaction) of cluster of differentiation 44(CD44),a cell adhesion molecule,were measured in 72-h-cultured SGC-7901 cells.RESULTS:Cell adhesion was promoted by IL-8(P = 0.001),but was inhibited by XTSJ decoction(P = 0.0001).Similarly,IL-8 promoted SGC-7901 cell invasion(P = 0.003),and XTSJ decoction inhibited cell invasion(P = 0.001).IL-8 induced SGC-7901 cell migration,but this was inhibited by XTSJ decoction.IL-8 up-regulated CD44 protein(P = 0.028) and m RNA expression(P = 0.002),whereas XTSJ decoction inhibited CD44 protein expression(P = 0.0001),but not m RNA expression(P = 0.275).An interaction between XTSJ decoction and IL-8 was confirmed in the invasion(P = 0.001) and CD44 m RNA expression of SGC-7901 cells(P = 0.010),but not in cell adhesion(P = 0.051).CONCLUSION:XTSJ decoction may inhibit adhesion,migration and invasion of gastric cancer cells,which is partly associated with down-regulation of IL-8.展开更多
AIM:To assess the diagnostic value of serum interleukin-8(IL-8)in the detection of colorectal cancer(CRC).METHODS:An original study was conducted to explore the potential value of IL-8 in CRC diagnosis.Receiver operat...AIM:To assess the diagnostic value of serum interleukin-8(IL-8)in the detection of colorectal cancer(CRC).METHODS:An original study was conducted to explore the potential value of IL-8 in CRC diagnosis.Receiver operating characteristic(ROC)analysis was performed and the area under the curve(AUC)value was calculated.PUBMED and EMBASE were searched(to October,2013),supplemented with manual screening for relevant publications.Meta-analysis methods were applied to pool sensitivity,specificity,positive and negative likelihood ratios,and diagnostic odds ratios and to construct a summary receiver-operating characteristic(s ROC)curve.Heterogeneity across studies was checked by the I2 test and Deek’s funnel plot method was applied to test publication bias.RESULTS:In our original study,serum IL-8 yielded an AUC of 0.742[95%CI:0.635-0.849].The sensitivity and specificity were 85.42%and 54.05%,respectively,at a cut-off value of 5.39.In this meta-analysis,we included five studies with 668 CRC patients and 374controls and one study in our own center with 48 CRC patients and 37 controls.The pooled sensitivity and specificity of IL-8 were 0.69(95%CI:0.42-0.87)and0.85(95%CI:0.68-0.94)for CRC detection.Besides,the area under the s ROC curve was 0.86(95%CI:0.82-0.88).Subgroup analysis suggested that there was no heterogeneity in the Asian subgroup but some in the European subgroup.In addition,no publication bias was found according to the Deek’s funnel plot asymmetry test.CONCLUSION:Serum IL-8 is a promising biomarker for CRC detection and may become a clinically useful tool to identify high-risk patients.展开更多
AIM:To evaluate(1) the association of the Helicobacter pylori(H.pylori) test and interleukin-8(IL-8) m RNA expression alone and the severity of gastric cancer(GC);(2) the association of both tests were added to patien...AIM:To evaluate(1) the association of the Helicobacter pylori(H.pylori) test and interleukin-8(IL-8) m RNA expression alone and the severity of gastric cancer(GC);(2) the association of both tests were added to patients' characteristics to identifli Thai suspected patients of gastric cancer who would receive the most benefit; and(3) diagnostic value of levels of IL-8 m RNA expression for gastric cancer.METHODS: A cross-sectional analytical study was completed with 220 patients with 86 GC patients who underwent endoscopy with gastric surgery divided into non-metastasis and metastasis groups,and 134 patients with benign lesions who underwent endoscopic examination,at the Gastrointestinal Surgery and Endoscopy Unit,Chiang Mai University Hospital between 2006 and 2010. Of 220 patients,86 cases of diagnosed gastric adenocarcinoma were in an advanced stage and 134 cases were non-cancer patients. RESULTS: The IL-8 m RNA expression showed predominant association with advanced GC when compared to H. pylori infection alone [OR(95%CI); 0.86(0.49-1.53) vs 5.44(3.08-9.62)] when including the patients' characteristics the highest of the area under the receiver operating characteristic curves(Au ROC) of the model were males older than 40 years of age [AuROC(95%CI); 0.81(0.75-0.86)]. However,preliminary testing for diagnostic indices of four cut-off points of IL-8 m RNA expression to predict the severity of GC cases found an increasing suboptimal trend from the likelihood ratio of positive to differentiate the severity in the GC group. The IL-8 mRNA expression showed a predominant association with GC when compared to H. pylori infection,especially in males older than 40 years of age who may benefit most from this test. CONCLUSION:The future research of IL-8 mRNA expression to predict severity in the gastric cancer group should be warranted.展开更多
AIM: To investigate the effect of interleukin-8(IL-8) on neural retinal ganglion cells(RGCs) and whether it can be alleviated by G31P. METHODS: RGC-5 cells were exposed to IL-8 with or without its specific receptor an...AIM: To investigate the effect of interleukin-8(IL-8) on neural retinal ganglion cells(RGCs) and whether it can be alleviated by G31P. METHODS: RGC-5 cells were exposed to IL-8 with or without its specific receptor antagonist G31P for 24h, and the cell viability was assessed by Cell Counting Kit 8(CCK-8). Apoptosis was measured by examining nuclear morphology and quantifying with flow cytometry. Reverse transcription quantitative real-time polymerase chain reaction(RT-qP CR) and Western blot were used to investigate the expression of apoptosis-related genes. RESULTS: CCK-8 assay showed that IL-8 significantly inhibits the viability of RGC-5 cells in a dose-dependent manner. Cell apoptosis assays exhibited higher apoptotic rate in IL-8 treatment group compared to control group. We further found that IL-8 could promote Bax and caspase-3 expressions, but decrease the level of Bcl-2 in the aspect of m RNA and protein. However, pre-treatment with G31P partly attenuated these effects in RGC-5 cells(P<0.05).CONCLUSION: These results indicate that anti-proliferation effects of IL-8 through induction of cell apoptosis regulated by Bcl-2, Bax and caspase-3 expressions, can be ameliorated by G31P.展开更多
Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its compl...Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its complications, but the relationship of its common variants with ACS has not been extensively studied.Methods We tested the hypothesis that variants in IL-8-251 A/T was associated with susceptibility to ACS and its recurrence in a Chinese case-control study comprising 675 patients with ACS and 636 control subjects and replicated the investigation in an independent study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.Results IL-8 -251A】T poly-morphism was associated with increased susceptibility to ACS (P=0.004;OR=1.30 CI:1.12-1.53).Replication in the second study yielded similar results.IL-8 -251 A/T may affect the expression of IL-8 by the evidence that augmented IL-8 production revealed in serum of the AMI patients by ELISA. Conclusions IL-8 -251 A/T polymorphism is associated with ACS risk in Chinese Han population and An allele of IL-8- 251A/T may be an independent predictive factor.展开更多
AIM:To detect the quantitative expression levels of the pro-inflammatory interleukin-8(IL8),antimicrobial peptides human beta defense-2(HBD2),and human beta defense-3(HBD3)genes in bacterial conjunctivitis.METHODS:The...AIM:To detect the quantitative expression levels of the pro-inflammatory interleukin-8(IL8),antimicrobial peptides human beta defense-2(HBD2),and human beta defense-3(HBD3)genes in bacterial conjunctivitis.METHODS:The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients.The genes expression levels were determined utilizing a reverse transcription quantitative polymerase chain reaction(RT-q PCR).The contribution of causative agent type,the number of isolates and severity of clinical features,in the increase of genes expression was also determined.RESULTS:The RT-q PCR showed that IL8,HBD2,and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control(P<0.001).In gram-negative bacterial conjunctivitis,HBD2 was highly up-regulated(P<0.001)compared to other types of bacterial conjunctivitis.In mixed bacterial conjunctivitis,a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed(P<0.05).The severity of clinical features was related to the up-regulation of IL8 and HBD2(P<0.05).CONCLUSION:IL8,HBD2,and HBD3 are immuneeffectors in infectious conjunctivitis.HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria.HBD3 is an obvious defender in different bacterial conjunctivitis.展开更多
AIM:To identify proangiogenic factors engaged in neovascular age-related macular degeneration(AMD)except vascular endothelial growth factor(VEGF)from human retinal pigment epithelial(h RPE)cells and investigate the un...AIM:To identify proangiogenic factors engaged in neovascular age-related macular degeneration(AMD)except vascular endothelial growth factor(VEGF)from human retinal pigment epithelial(h RPE)cells and investigate the underlying mechanisms.METHODS:VEGF receptor 2(VEGFR2)in ARPE-19 cells was depleted by si RNA transfection or overexpressed through adenovirus infection.The m RNA and the protein levels of interleukin-8(IL-8)in ARPE-19 cells were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively.The protein levels of AKT,p-AKT,MEK,p-MEK,ERK1/2,p-ERK1/2,JNK,p-JNK,p38 and p-p38 were detected by Western blotting.A selective chemical inhibitor,LY3214996,was employed to inhibit phosphorylation of ERK1/2.Cell viability was determined by MTT assay.RESULTS:Knockdown of VEGFR2 in ARPE-19 cells robustly augmented IL-8 production at both the m RNA and the protein levels.Silencing VEGFR2 substantially enhanced phosphorylation of MEK and ERK1/2 while exerted no effects on phosphorylation of AKT,JNK and p38.Inhibiting ERK1/2 phosphorylation by LY3214996 reversed changes in VEGFR2 knockdown-induced IL-8 upregulation at the m RNA and the protein levels with no effects on cell viability.VEGFR2 overexpression significantly reduced IL-8 generation at the m RNA and the protein levels.CONCLUSION:Blockade of VEGF signaling augments IL-8 secretion via MEK/ERK1/2 axis and overactivation of VEGF pathway decreases IL-8 production in h RPE cells.Upregulated IL-8 expression after VEGF signaling inhibition in h RPE cells may be responsible for being incompletely responsive to anti-VEGF remedy in neovascular AMD,and IL-8 may serve as an alternative therapeutic target for neovascular AMD.展开更多
The development and maintenance of an abundant blood supply is essential for the healing of wound and neoplastic tissues.Angiogenesis,the development of new vessels from adjacent capillary networks,plays an important ...The development and maintenance of an abundant blood supply is essential for the healing of wound and neoplastic tissues.Angiogenesis,the development of new vessels from adjacent capillary networks,plays an important role in physiologic and as well as in展开更多
Train drivers are engaged in high-stress job. It may induce sleep, fatigue, and alertness loss at work, and endanger public safety. It’s unclear that cytokines of train driver would be influenced by their job. The re...Train drivers are engaged in high-stress job. It may induce sleep, fatigue, and alertness loss at work, and endanger public safety. It’s unclear that cytokines of train driver would be influenced by their job. The research considers the hypothesis that stressful professions, such as train driver, influence the body’s immune system through the long-time and high-pressure working, and change production of neuro-immune factors. Using enzyme linked immunosorbent assay (ELISA), several neuro-immune factors were assayed among train drivers (N = 82) and health blood donors (N = 80) enrolled in the Yunnan Collaborative Innovation Center for Public Health and Disease Control. The concentrations of angiotensin, C-reactive protein (CRP), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) were determined. Kruskal-Wallis test and Dunn’s multiple comparisons test were performed for overall comparison between groups and for pairwise comparison, respectively. Statistical significance level was set at P < 0.05. The profession of train driving was not associated with significant increases or decreases in the systemic levels of inflammatory (CRP, IL-8, and TNF-α), but it was associated with the high expression of angiotensin in vivo. These findings suggest that the job of train driving may not be associated with significant alterations in systemic immune condition, but arouse the level of angiotensin.展开更多
Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues follo...Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of Gα12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in Gα12-silenced (si-Gα12) and inducible QLα12 (constitutively active Gα12) Madin-Darby Canine Kidney (QLα12-MDCK) cell lines after H2O2/catalase cell injury. QLα12- and si-Gα12 MDCK cells showed time-, agonist- and Gα12-dependent increases in IL-8 mRNA and protein. Gα12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QLα12γGTCre+, proximal tubule Qα12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in Gα12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QLα12γGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated Gα12 and renal injury. Gα12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting Gα12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery.展开更多
AIM:To investigate the relationship between Interleukin-8 (IL-8) and proliferation,adhesion,migration,invasion and chemosensitivity of gastric cancer (GC) cells.METHODS:The IL-8 cDNA was stably transfected into human ...AIM:To investigate the relationship between Interleukin-8 (IL-8) and proliferation,adhesion,migration,invasion and chemosensitivity of gastric cancer (GC) cells.METHODS:The IL-8 cDNA was stably transfected into human GC cell line MKN-45 and selected IL-8-secreting transfectants.The expression of IL-8 in human GC cell line KATO-Ⅲ was inhibited by RNA interference.The expressions of mRNA and protein of IL-8 in GC cells were detected by real-time reverse transcriptionpolymerase chain reaction or enzyme-linked immunosorbent assay (ELISA).RESULTS:The overexpression of IL-8 resulted in an increased cell adhesion,migration and invasion,and a significant resistance to oxaliplatin in MKN-45 cells.Inhibition of IL-8 expression with small interfering RNA decreased the adhesion,migration and invasion functions and oxaliplatin resistance in KATO-Ⅲ cells.IL-8 increased NF-κB and Akt activities and adhesion molecules ICAM-1,VCAM-1,and CD44 expression in GC cells.CONCLUSION:Overexpression of IL-8 promotes the adhesion,migration,invasion,and chemoresistance of GC cells,indicating that IL-8 is an important therapeutic target in GC.展开更多
AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochem...AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.展开更多
AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-a (TNF-a) on intestinal epithelial cells. METHODS: Caco-2 cells were incubated with TNF-a alone or in the p...AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-a (TNF-a) on intestinal epithelial cells. METHODS: Caco-2 cells were incubated with TNF-a alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 (IL-8) secretion by intestinal epithelial cells was measured using an ELISA. Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase (ERK), anti-phospho- ERK and anti-IκB-a. RESULTS: A TNF-a-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF- a-induced IL-8 secretion was reduced by L. plantarum. L. plantarum inhibited the activation of ERK and the degradation of IκB-a in TNF-a-treated Caco-2 cells. CONCLUSION: Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-a is inhibited by L. plantarum. Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway.展开更多
AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopol...AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide (HpyloriSS1-LPS). METHODS: SGC-7901 cells were treated with Hpylori SS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant recovered from LBG culture MRS broth (LBG-S). Cellular lysates were prepared for Western blot with anti-TLR4, anti-transforming growth factor β-activated kinase 1 (TAK1), anti-phospho-TAK1, anti-nuclear factor κB (NF-κB), anti-p38 mitogen-activated protein kinase (p38MAPK), and anti-phospho-p38MAPK antibodies. The amount of IL-8 in cell culture medium was measured by ELISA. RESULTS: H pylori SS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAK1, subsequently enhanced the activation of NF- κB and the phosphorylation of p38MAPK in a time- dependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-S pretreatment attenuated the expression of TLR4, inhibited the phosphorylation of TAK1 and p38MAPK, prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION: H pylori SS1-LPS induces IL-8 production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-S prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.展开更多
AIM: To explore the effect of Astragalus mongholicus polysaccharide (APS) on gene expression and mitogenactivated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were ...AIM: To explore the effect of Astragalus mongholicus polysaccharide (APS) on gene expression and mitogenactivated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were divided into control group, lipopolysaccharide (LPS) group, LPS+ 50 μg/mL APS group, LPS+ 100 μg/mL APS group, LPS+ 200 μg/mL APS group, and LPS+ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor (TNF)-α and interleukin (IL)-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS: The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signalregulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION: APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment ofintestinal inflammation.展开更多
AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8-251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. METHODS: Peripheral blood samples of 255 normal ...AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8-251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. METHODS: Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8-251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ 2 tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. RESULTS: On comparing the frequencies of genotypesof patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69,P = 0.003). CONCLUSION: Variant allele and genotype of IL-8 (-251 T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.展开更多
we d.termlned amniotic fluid and blood IL-6, 8 concentrations or so pregnancy womenwith premature rupture of membrane,(PROM) by ELISA - e^led the fetal membranes by.pathology. The results showed that there were 36 pet...we d.termlned amniotic fluid and blood IL-6, 8 concentrations or so pregnancy womenwith premature rupture of membrane,(PROM) by ELISA - e^led the fetal membranes by.pathology. The results showed that there were 36 petients with intraamnio infection (IAI) and theirIL-6.IL-8 concentrations were significantly higher than those of the patients without IAI. In 20 ofthe 36 patients their neonates Apgar scores≤7 and their fluid- blood IL-6.IL-8 cooreuthed.were significently higher htat those. of other 16 patients whose Apgar scores≥8.These results ndicated that the bkood and amnioiotic fluid IL-6. IL-8 concentrations of pregnancy wom-en with PROM would help to predict and esimate fetus展开更多
Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression ...Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α (IL-1α) and -8 (IL-8) in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF (P=0.014) and IL-1α (P=0.049) expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential (PUNLMP) (P=0.000) and carcinoma (P=0.009) whilst IL-1α (P=0.000 and P=0.000 respectively) and IL-8 (P=0.000 and P=0.023 respectively) expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP (P=0.049, r=-0.578) as well as in tumour grouping (P=0.033, r=-0.276). Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.展开更多
AIM:To investigate genetic diversity of Helicobacter pylori (H.pylori) cell division-related gene A (cdrA) and its effect on the host response.METHODS:Inactivation of H.pylori cdrA,which is involved in cell division a...AIM:To investigate genetic diversity of Helicobacter pylori (H.pylori) cell division-related gene A (cdrA) and its effect on the host response.METHODS:Inactivation of H.pylori cdrA,which is involved in cell division and morphological elongation,has a role in chronic persistent infections.Genetic property of H.pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients,respectively.Enzyme-linked immunosorbent assay was performed to measure interleukin-8 (IL-8) secretion with gastric biopsy specimens obtained from American patients colonized with cdrA-positive or-negative strains and AGS cells cocultured with wild-type HPK5 (cdrA-positive) or its derivative HPKT510 (cdrA-disruptant).Furthermore,the cytotoxin-associated gene A (cagA) status (translocation and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-κB) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5,HPKT510 and its derivative HPK5CA (cagA disruptant) by western blotting analysis with immunoprecipitation.RESULTS:Genetic diversity of the H.pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types,cdrA-positive (allele types;Ⅰand Ⅱ) and cdrA-negative (allele types;Ⅲ and Ⅳ) categories,respectively.Almost all Japanese isolates were cdrA-positive (Ⅰ:7.8% and Ⅱ:90.2%),whereas 16.9% of American isolates were cdrA-positive (Ⅱ) and 83.1% were cdrA-negative (Ⅲ:37.7% and Ⅳ:45.5%),indicating extended diversity of cdrA in individual American isolates.Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases.However,12 cases had a different cdrA allele and 6 of them exhibited a different cdrA category between two regions in the stomach.Furthermore,in 5 of the 6 cases possessing a different cdrA category,cdrA-negative isolate existed in the corpus,suggesting that cdrA-negative strain is more adaptable to colonization in the corpus.IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower (P < 0.01) compared to wildtype HPK5:corresponding to 50%-60% of those of wild-type HPK5.These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL,respectively.Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation,however,nuclear accumulation of NF-κB was lower by HPKT510 compared to HPK5.CONCLUSION:Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB,and hence,attenuate the host immunity leading to persistent infection.展开更多
基金Supported by A research grant,No.0720570,from the National Cancer Center,by the National Research Foundation of Korea(NRF)grant,Basic Research Program,No.2010-0009910MRCfor Gene Regulation,No.2011-0030132 funded by the Korea government(MSIP)
文摘Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer development and progression.Interleukin-8(IL-8)is overexpressed in gastric mucosa exposed to H.pylori.The expression of IL-8 directly correlates with a poor prognosis in gastric cancer.IL-8 is multifunctional.In addition to its potent chemotactic activity,it can induce proliferation and migration of cancer cells.In this review,we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer.The relationship between IL-8 and H.pylori is discussed.We also summarize the current therapeutics against IL-8 in gastric cancer.
基金Supported by grant from the three-year action plan fund of Traditional Chinese Medicine,Shanghai City Health Administration,China,No.ZYSNXD-CC-ZDYJ024
文摘AIM:To investigate the interaction between Xiaotan Sanjie(XTSJ) decoction and interleukin-8(IL-8) and its effect on adhesion,migration and invasion of SGC-7901 gastric cancer cells.METHODS:SGC-7901 gastric cancer cells were exposed to serum containing XTSJ decoction and/orIL-8(1 ng/m L).SGC-7901 cell adhesion to fibronectin,an extracellular matrix component,was detected using the Cell Counting Kit-8.Migration and invasion abilities of SGC-7901 cells were detected by scratch wound and Transwell chamber assays.Then,protein(immunofluorescence and Western blot) and m RNA levels(quantitative polymerase chain reaction) of cluster of differentiation 44(CD44),a cell adhesion molecule,were measured in 72-h-cultured SGC-7901 cells.RESULTS:Cell adhesion was promoted by IL-8(P = 0.001),but was inhibited by XTSJ decoction(P = 0.0001).Similarly,IL-8 promoted SGC-7901 cell invasion(P = 0.003),and XTSJ decoction inhibited cell invasion(P = 0.001).IL-8 induced SGC-7901 cell migration,but this was inhibited by XTSJ decoction.IL-8 up-regulated CD44 protein(P = 0.028) and m RNA expression(P = 0.002),whereas XTSJ decoction inhibited CD44 protein expression(P = 0.0001),but not m RNA expression(P = 0.275).An interaction between XTSJ decoction and IL-8 was confirmed in the invasion(P = 0.001) and CD44 m RNA expression of SGC-7901 cells(P = 0.010),but not in cell adhesion(P = 0.051).CONCLUSION:XTSJ decoction may inhibit adhesion,migration and invasion of gastric cancer cells,which is partly associated with down-regulation of IL-8.
文摘AIM:To assess the diagnostic value of serum interleukin-8(IL-8)in the detection of colorectal cancer(CRC).METHODS:An original study was conducted to explore the potential value of IL-8 in CRC diagnosis.Receiver operating characteristic(ROC)analysis was performed and the area under the curve(AUC)value was calculated.PUBMED and EMBASE were searched(to October,2013),supplemented with manual screening for relevant publications.Meta-analysis methods were applied to pool sensitivity,specificity,positive and negative likelihood ratios,and diagnostic odds ratios and to construct a summary receiver-operating characteristic(s ROC)curve.Heterogeneity across studies was checked by the I2 test and Deek’s funnel plot method was applied to test publication bias.RESULTS:In our original study,serum IL-8 yielded an AUC of 0.742[95%CI:0.635-0.849].The sensitivity and specificity were 85.42%and 54.05%,respectively,at a cut-off value of 5.39.In this meta-analysis,we included five studies with 668 CRC patients and 374controls and one study in our own center with 48 CRC patients and 37 controls.The pooled sensitivity and specificity of IL-8 were 0.69(95%CI:0.42-0.87)and0.85(95%CI:0.68-0.94)for CRC detection.Besides,the area under the s ROC curve was 0.86(95%CI:0.82-0.88).Subgroup analysis suggested that there was no heterogeneity in the Asian subgroup but some in the European subgroup.In addition,no publication bias was found according to the Deek’s funnel plot asymmetry test.CONCLUSION:Serum IL-8 is a promising biomarker for CRC detection and may become a clinically useful tool to identify high-risk patients.
文摘AIM:To evaluate(1) the association of the Helicobacter pylori(H.pylori) test and interleukin-8(IL-8) m RNA expression alone and the severity of gastric cancer(GC);(2) the association of both tests were added to patients' characteristics to identifli Thai suspected patients of gastric cancer who would receive the most benefit; and(3) diagnostic value of levels of IL-8 m RNA expression for gastric cancer.METHODS: A cross-sectional analytical study was completed with 220 patients with 86 GC patients who underwent endoscopy with gastric surgery divided into non-metastasis and metastasis groups,and 134 patients with benign lesions who underwent endoscopic examination,at the Gastrointestinal Surgery and Endoscopy Unit,Chiang Mai University Hospital between 2006 and 2010. Of 220 patients,86 cases of diagnosed gastric adenocarcinoma were in an advanced stage and 134 cases were non-cancer patients. RESULTS: The IL-8 m RNA expression showed predominant association with advanced GC when compared to H. pylori infection alone [OR(95%CI); 0.86(0.49-1.53) vs 5.44(3.08-9.62)] when including the patients' characteristics the highest of the area under the receiver operating characteristic curves(Au ROC) of the model were males older than 40 years of age [AuROC(95%CI); 0.81(0.75-0.86)]. However,preliminary testing for diagnostic indices of four cut-off points of IL-8 m RNA expression to predict the severity of GC cases found an increasing suboptimal trend from the likelihood ratio of positive to differentiate the severity in the GC group. The IL-8 mRNA expression showed a predominant association with GC when compared to H. pylori infection,especially in males older than 40 years of age who may benefit most from this test. CONCLUSION:The future research of IL-8 mRNA expression to predict severity in the gastric cancer group should be warranted.
文摘AIM: To investigate the effect of interleukin-8(IL-8) on neural retinal ganglion cells(RGCs) and whether it can be alleviated by G31P. METHODS: RGC-5 cells were exposed to IL-8 with or without its specific receptor antagonist G31P for 24h, and the cell viability was assessed by Cell Counting Kit 8(CCK-8). Apoptosis was measured by examining nuclear morphology and quantifying with flow cytometry. Reverse transcription quantitative real-time polymerase chain reaction(RT-qP CR) and Western blot were used to investigate the expression of apoptosis-related genes. RESULTS: CCK-8 assay showed that IL-8 significantly inhibits the viability of RGC-5 cells in a dose-dependent manner. Cell apoptosis assays exhibited higher apoptotic rate in IL-8 treatment group compared to control group. We further found that IL-8 could promote Bax and caspase-3 expressions, but decrease the level of Bcl-2 in the aspect of m RNA and protein. However, pre-treatment with G31P partly attenuated these effects in RGC-5 cells(P<0.05).CONCLUSION: These results indicate that anti-proliferation effects of IL-8 through induction of cell apoptosis regulated by Bcl-2, Bax and caspase-3 expressions, can be ameliorated by G31P.
文摘Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its complications, but the relationship of its common variants with ACS has not been extensively studied.Methods We tested the hypothesis that variants in IL-8-251 A/T was associated with susceptibility to ACS and its recurrence in a Chinese case-control study comprising 675 patients with ACS and 636 control subjects and replicated the investigation in an independent study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.Results IL-8 -251A】T poly-morphism was associated with increased susceptibility to ACS (P=0.004;OR=1.30 CI:1.12-1.53).Replication in the second study yielded similar results.IL-8 -251 A/T may affect the expression of IL-8 by the evidence that augmented IL-8 production revealed in serum of the AMI patients by ELISA. Conclusions IL-8 -251 A/T polymorphism is associated with ACS risk in Chinese Han population and An allele of IL-8- 251A/T may be an independent predictive factor.
文摘AIM:To detect the quantitative expression levels of the pro-inflammatory interleukin-8(IL8),antimicrobial peptides human beta defense-2(HBD2),and human beta defense-3(HBD3)genes in bacterial conjunctivitis.METHODS:The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients.The genes expression levels were determined utilizing a reverse transcription quantitative polymerase chain reaction(RT-q PCR).The contribution of causative agent type,the number of isolates and severity of clinical features,in the increase of genes expression was also determined.RESULTS:The RT-q PCR showed that IL8,HBD2,and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control(P<0.001).In gram-negative bacterial conjunctivitis,HBD2 was highly up-regulated(P<0.001)compared to other types of bacterial conjunctivitis.In mixed bacterial conjunctivitis,a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed(P<0.05).The severity of clinical features was related to the up-regulation of IL8 and HBD2(P<0.05).CONCLUSION:IL8,HBD2,and HBD3 are immuneeffectors in infectious conjunctivitis.HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria.HBD3 is an obvious defender in different bacterial conjunctivitis.
基金Supported by the National Natural Science Foundation of China(No.81200670)。
文摘AIM:To identify proangiogenic factors engaged in neovascular age-related macular degeneration(AMD)except vascular endothelial growth factor(VEGF)from human retinal pigment epithelial(h RPE)cells and investigate the underlying mechanisms.METHODS:VEGF receptor 2(VEGFR2)in ARPE-19 cells was depleted by si RNA transfection or overexpressed through adenovirus infection.The m RNA and the protein levels of interleukin-8(IL-8)in ARPE-19 cells were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively.The protein levels of AKT,p-AKT,MEK,p-MEK,ERK1/2,p-ERK1/2,JNK,p-JNK,p38 and p-p38 were detected by Western blotting.A selective chemical inhibitor,LY3214996,was employed to inhibit phosphorylation of ERK1/2.Cell viability was determined by MTT assay.RESULTS:Knockdown of VEGFR2 in ARPE-19 cells robustly augmented IL-8 production at both the m RNA and the protein levels.Silencing VEGFR2 substantially enhanced phosphorylation of MEK and ERK1/2 while exerted no effects on phosphorylation of AKT,JNK and p38.Inhibiting ERK1/2 phosphorylation by LY3214996 reversed changes in VEGFR2 knockdown-induced IL-8 upregulation at the m RNA and the protein levels with no effects on cell viability.VEGFR2 overexpression significantly reduced IL-8 generation at the m RNA and the protein levels.CONCLUSION:Blockade of VEGF signaling augments IL-8 secretion via MEK/ERK1/2 axis and overactivation of VEGF pathway decreases IL-8 production in h RPE cells.Upregulated IL-8 expression after VEGF signaling inhibition in h RPE cells may be responsible for being incompletely responsive to anti-VEGF remedy in neovascular AMD,and IL-8 may serve as an alternative therapeutic target for neovascular AMD.
基金supported by grant from National Natural Science Foundation of China No10772127,30570450Program for New Century Excellent Talents in University NCET-06-0789Sichaun Youth Science and Technology Foundation 06ZQ026-009
文摘The development and maintenance of an abundant blood supply is essential for the healing of wound and neoplastic tissues.Angiogenesis,the development of new vessels from adjacent capillary networks,plays an important role in physiologic and as well as in
文摘Train drivers are engaged in high-stress job. It may induce sleep, fatigue, and alertness loss at work, and endanger public safety. It’s unclear that cytokines of train driver would be influenced by their job. The research considers the hypothesis that stressful professions, such as train driver, influence the body’s immune system through the long-time and high-pressure working, and change production of neuro-immune factors. Using enzyme linked immunosorbent assay (ELISA), several neuro-immune factors were assayed among train drivers (N = 82) and health blood donors (N = 80) enrolled in the Yunnan Collaborative Innovation Center for Public Health and Disease Control. The concentrations of angiotensin, C-reactive protein (CRP), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) were determined. Kruskal-Wallis test and Dunn’s multiple comparisons test were performed for overall comparison between groups and for pairwise comparison, respectively. Statistical significance level was set at P < 0.05. The profession of train driving was not associated with significant increases or decreases in the systemic levels of inflammatory (CRP, IL-8, and TNF-α), but it was associated with the high expression of angiotensin in vivo. These findings suggest that the job of train driving may not be associated with significant alterations in systemic immune condition, but arouse the level of angiotensin.
文摘Acute kidney injury (AKI) is common in hospitalized patients and is strongly correlated with increased morbidity, mortality, and prolonged hospitalization. However, signals that determine whether injured tissues following AKI will repair or fibrose and lead to chronic kidney disease (CKD) are not well defined. Numerous cytokines are activated at various times after injury and recruit inflammatory cells. Interleukin-8 (IL-8) is upregulated following activation of Gα12 by H2O2, a reactive oxygen species (ROS). Herein, we study this occurrence in vitro and in vivo. IL-8 was measured by ELISA in Gα12-silenced (si-Gα12) and inducible QLα12 (constitutively active Gα12) Madin-Darby Canine Kidney (QLα12-MDCK) cell lines after H2O2/catalase cell injury. QLα12- and si-Gα12 MDCK cells showed time-, agonist- and Gα12-dependent increases in IL-8 mRNA and protein. Gα12-silenced MDCK cells demonstrated lower IL-8 expression and blunted IL-8 increases. In transgenic mice (QLα12γGTCre+, proximal tubule Qα12 expression) ischemia reperfusion injury led to significant upregulation of CXCL-1 (IL-8 homologue) at 48 hours that was not observed in Gα12 knockout mice. Macrophages in renal cells from these mice were imaged by immunofluorescent microscopy and QLα12γGTCre+ showed increased macrophage infiltration. We demonstrate that IL-8 is a critical link between H2O2 stimulated Gα12 and renal injury. Gα12 activation led to increased IL-8 expression, a potent mediator of inflammation after injury. Future studies targeting Gα12 for inhibition after injury may blunt the IL-8 response and allow for organ recovery.
基金Supported by The Fund of Nanjing Medical University Science and Technology Development,No.09NJMUZ30
文摘AIM:To investigate the relationship between Interleukin-8 (IL-8) and proliferation,adhesion,migration,invasion and chemosensitivity of gastric cancer (GC) cells.METHODS:The IL-8 cDNA was stably transfected into human GC cell line MKN-45 and selected IL-8-secreting transfectants.The expression of IL-8 in human GC cell line KATO-Ⅲ was inhibited by RNA interference.The expressions of mRNA and protein of IL-8 in GC cells were detected by real-time reverse transcriptionpolymerase chain reaction or enzyme-linked immunosorbent assay (ELISA).RESULTS:The overexpression of IL-8 resulted in an increased cell adhesion,migration and invasion,and a significant resistance to oxaliplatin in MKN-45 cells.Inhibition of IL-8 expression with small interfering RNA decreased the adhesion,migration and invasion functions and oxaliplatin resistance in KATO-Ⅲ cells.IL-8 increased NF-κB and Akt activities and adhesion molecules ICAM-1,VCAM-1,and CD44 expression in GC cells.CONCLUSION:Overexpression of IL-8 promotes the adhesion,migration,invasion,and chemoresistance of GC cells,indicating that IL-8 is an important therapeutic target in GC.
基金Supported by The National Key Project of Scientific and Technical Supporting Programs of China, No. 2006BAI02A14National Natural Science Foundation of China, No. 30770996 and No. 30901776
文摘AIM: To investigate the value of interleukin-8 (IL-8), a pro-inflammatory chemokine, in predicting the prognosis of pancreatic cancer. METHODS: Expression of IL-8 and its receptor CXCR1 was assessed by immunohistochemistry in pancreatic cancer and chronic pancreatitis samples. Enzyme-linked immunosorbent assay was used to detect the serum IL-8 levels in pancreatic cancer patients. Human pancreatic cancer tissues were heterotopically transplanted to the immune-deficiency mice to evaluate the effect of serum IL-8 on the tumorigenesis of the cancer samples.RESULTS: IL-8 and CXCR1 proteins were both overexpressed in pancreatic adenocarcinoma samples (55.6% and 65.4%, respectively) compared with the matched para-cancer tissues (25.9% and 12.3%, P < 0.01), or chronic pancreatitis (0% and 25%, P < 0.05). Serum IL-8 levels in pancreatic cancer patients (271.1 ± 187.7 ng/mL) were higher than in other digestive system tumors, such as gastric cancer (41.77 ± 9.11 ng/mL, P = 0.025), colorectal carcinoma (78.72 ± 80.60 ng/mL, P = 0.032) and hepatocellular carcinoma (59.60 ± 19.80 ng/mL, P = 0.016). In vivo tumorigenesis analysis further proved that tumor tissues from patients with higher serum IL-8 levels grew faster than those with lower IL-8 levels. CONCLUSION: IL-8 can be a fine serum marker for predicting the prognosis pancreatic cancer.
基金Supported by grant No. 0520050040 from the Seoul National University Hospital Research Fund and by KT&G Reserach Fund
文摘AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-a (TNF-a) on intestinal epithelial cells. METHODS: Caco-2 cells were incubated with TNF-a alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 (IL-8) secretion by intestinal epithelial cells was measured using an ELISA. Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase (ERK), anti-phospho- ERK and anti-IκB-a. RESULTS: A TNF-a-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF- a-induced IL-8 secretion was reduced by L. plantarum. L. plantarum inhibited the activation of ERK and the degradation of IκB-a in TNF-a-treated Caco-2 cells. CONCLUSION: Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-a is inhibited by L. plantarum. Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway.
基金Basic Research Project of Science and Technology Offi ce of Sichuan Province, No. 04JY029-090-1
文摘AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide (HpyloriSS1-LPS). METHODS: SGC-7901 cells were treated with Hpylori SS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant recovered from LBG culture MRS broth (LBG-S). Cellular lysates were prepared for Western blot with anti-TLR4, anti-transforming growth factor β-activated kinase 1 (TAK1), anti-phospho-TAK1, anti-nuclear factor κB (NF-κB), anti-p38 mitogen-activated protein kinase (p38MAPK), and anti-phospho-p38MAPK antibodies. The amount of IL-8 in cell culture medium was measured by ELISA. RESULTS: H pylori SS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAK1, subsequently enhanced the activation of NF- κB and the phosphorylation of p38MAPK in a time- dependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-S pretreatment attenuated the expression of TLR4, inhibited the phosphorylation of TAK1 and p38MAPK, prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION: H pylori SS1-LPS induces IL-8 production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-S prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.
文摘AIM: To explore the effect of Astragalus mongholicus polysaccharide (APS) on gene expression and mitogenactivated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were divided into control group, lipopolysaccharide (LPS) group, LPS+ 50 μg/mL APS group, LPS+ 100 μg/mL APS group, LPS+ 200 μg/mL APS group, and LPS+ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor (TNF)-α and interleukin (IL)-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS: The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signalregulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION: APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment ofintestinal inflammation.
基金Supported by USM Research University Grant, No. 1001/PPSP/812032
文摘AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8-251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. METHODS: Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8-251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ 2 tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. RESULTS: On comparing the frequencies of genotypesof patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69,P = 0.003). CONCLUSION: Variant allele and genotype of IL-8 (-251 T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.
文摘we d.termlned amniotic fluid and blood IL-6, 8 concentrations or so pregnancy womenwith premature rupture of membrane,(PROM) by ELISA - e^led the fetal membranes by.pathology. The results showed that there were 36 petients with intraamnio infection (IAI) and theirIL-6.IL-8 concentrations were significantly higher than those of the patients without IAI. In 20 ofthe 36 patients their neonates Apgar scores≤7 and their fluid- blood IL-6.IL-8 cooreuthed.were significently higher htat those. of other 16 patients whose Apgar scores≥8.These results ndicated that the bkood and amnioiotic fluid IL-6. IL-8 concentrations of pregnancy wom-en with PROM would help to predict and esimate fetus
基金sponsored in part by Science and Technology Commission of Shanghai Municipality, China (No. 07ZR14018)
文摘Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α (IL-1α) and -8 (IL-8) in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF (P=0.014) and IL-1α (P=0.049) expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential (PUNLMP) (P=0.000) and carcinoma (P=0.009) whilst IL-1α (P=0.000 and P=0.000 respectively) and IL-8 (P=0.000 and P=0.023 respectively) expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP (P=0.049, r=-0.578) as well as in tumour grouping (P=0.033, r=-0.276). Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.
基金Supported by The Project Research Fund from Kochi University,to Takeuchi Ha Grant-in-Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan,No. 21590631 and 21590629,in part
文摘AIM:To investigate genetic diversity of Helicobacter pylori (H.pylori) cell division-related gene A (cdrA) and its effect on the host response.METHODS:Inactivation of H.pylori cdrA,which is involved in cell division and morphological elongation,has a role in chronic persistent infections.Genetic property of H.pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients,respectively.Enzyme-linked immunosorbent assay was performed to measure interleukin-8 (IL-8) secretion with gastric biopsy specimens obtained from American patients colonized with cdrA-positive or-negative strains and AGS cells cocultured with wild-type HPK5 (cdrA-positive) or its derivative HPKT510 (cdrA-disruptant).Furthermore,the cytotoxin-associated gene A (cagA) status (translocation and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-κB) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5,HPKT510 and its derivative HPK5CA (cagA disruptant) by western blotting analysis with immunoprecipitation.RESULTS:Genetic diversity of the H.pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types,cdrA-positive (allele types;Ⅰand Ⅱ) and cdrA-negative (allele types;Ⅲ and Ⅳ) categories,respectively.Almost all Japanese isolates were cdrA-positive (Ⅰ:7.8% and Ⅱ:90.2%),whereas 16.9% of American isolates were cdrA-positive (Ⅱ) and 83.1% were cdrA-negative (Ⅲ:37.7% and Ⅳ:45.5%),indicating extended diversity of cdrA in individual American isolates.Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases.However,12 cases had a different cdrA allele and 6 of them exhibited a different cdrA category between two regions in the stomach.Furthermore,in 5 of the 6 cases possessing a different cdrA category,cdrA-negative isolate existed in the corpus,suggesting that cdrA-negative strain is more adaptable to colonization in the corpus.IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower (P < 0.01) compared to wildtype HPK5:corresponding to 50%-60% of those of wild-type HPK5.These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL,respectively.Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation,however,nuclear accumulation of NF-κB was lower by HPKT510 compared to HPK5.CONCLUSION:Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB,and hence,attenuate the host immunity leading to persistent infection.
