The protective ability of host defense system is largely dependent on germ-line encoded pattern-recogni-tion receptors(PRRs).These PRRs respond to a variety of exogenous pathogens or endogenous danger signals,by recog...The protective ability of host defense system is largely dependent on germ-line encoded pattern-recogni-tion receptors(PRRs).These PRRs respond to a variety of exogenous pathogens or endogenous danger signals,by recognizing some highly conserved structures such as pathogen-associated molecular patterns(PAMPs)and danger/damage associated molecular patterns(DAMPs).The most studied PRRs are Toll-like receptors(TLRs).Activation of TLRs triggers production of inflammatory cytokines and type I interferons(IFNs)via myeloid differentiation primary response gene 88(MyD88)-depen-dent or-independent signaling respectively,thereby modulating innate and adaptive immunity,as well as inflammatory responses.This review introduces the classification,structure,and specific ligands of TLRs,and focuses on their signal pathways and biological activities,as well as clinical relevance.These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases,including tuberculosis(TB),microbial keratitis,and hepatitis B and C.展开更多
E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx(...E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx(sLex).Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode.Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLex and a glycomimetic antagonist thereof reveal an extended E-selectin conformation,which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations.Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution.This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment.The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists.This is of special interest,since their therapeutic potentialwas recently demonstrated with the pan-selectin antagonists GMI-1070(Rivipansel).展开更多
The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3(Tim-3)mRNA peripheral blood lymphocytes isolated from asthmaticin patients and to exami...The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3(Tim-3)mRNA peripheral blood lymphocytes isolated from asthmaticin patients and to examine the correlation among Tim-3 mRNA,interleukin-4(IL-4),interferon-γ(IFN-γ)level,and FEV1/FVC(force expiratory volume in one second/forced vital capacity)to explore the role of Tim-3 in the development and progression of asthmatic inflammation.Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction(RT-PCR).The IL-4 and IFN-γlevels were determined by using enzyme-linked immunosorbent assay(ELISA).The correlation among Tim-3 mRNA,IL-4,IFN-γlevel,and pulmonary ventilatory capacity was analyzed.The expres-sion of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39�0.06,significantly higher than that in patients at the remission stage and controls(0.18�0.05 and 0.07�0.03,P<0.05).The level of IL-4 in patients with acute asthma exacerbation was 68.42�10.54,significantly higher than that in the patients at the remission stage and controls(41.83�9.37 and 32.75�8.16,P<0.05).The level of IL-4 in patients in remission was significantly higher than that in controls(P<0.05).The level of IFN-γin patients with acute asthma exacerbation was 65.74�7.85,significantly lower than that in patients in remission and the control group(120.84�11.62 and 139.65�13.47,P<0.05).The level of IFN-γin patients in asthma remission was significantly lower than that in controls(P<0.05).Tim-3 mRNA expression was positively correlated with the level of IL-4(r=0.68,P<0.05)and negatively with the level of IFN-γand pulmonary ventilatory capacity(r=–0.85,r=–0.76,both P<0.01).The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation.展开更多
The role of high sensitivity C-reactive protein(hsCRP)in predicting prognosis after stroke in the Asian population has not been investigated.We hypothesized that elevated levels of hsCRP were associated with worsening...The role of high sensitivity C-reactive protein(hsCRP)in predicting prognosis after stroke in the Asian population has not been investigated.We hypothesized that elevated levels of hsCRP were associated with worsening prognosis after stroke in Chinese patients.Two hundred and ninety consecutive patients withfirst-onset stroke and 290 age-and gender-matched control subjects without any cerebrovascular disease were enrolled for study.Plasma hsCRP level was detected and subsequent vascular events and death were recorded in both groups over a 5-year period.Compared to control group,patients presenting with stroke had higher plasma hsCRP level(3.3±3.8 vs 1.3±2.2 mg/L,P<0.01).Furthermore,in the group of patients with stroke,the mean plasma hsCRP level was higher in patients who developed subsequent vascular diseases or died as compared with the patients without further complications(4.4±4.3 vs 2.7±3.3 mg/L,P<0.01).Compared to the lowest tertile of hsCRP level,the relative risk for vascular events or death in stroke patients was 2.91 in the highest tertile of hsCRP(95%CI,1.54–5.50,P=0.001).This increase in relative risk for vascular events or death in stroke patients continued after adjustment for age,sex and other cardiovascular risk factors such as hypertension and diabetes(OR:2.771,95%CI:1.367–5.617,P=0.005).Thesefindings indicate that increased hsCRP level is associated with worsening prognosis after stroke in Chinese patients and suggests that inflammation is correlated with stroke outcome.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.30972763 and U0832006)American NIH grant(No.5R01EY19021).
文摘The protective ability of host defense system is largely dependent on germ-line encoded pattern-recogni-tion receptors(PRRs).These PRRs respond to a variety of exogenous pathogens or endogenous danger signals,by recognizing some highly conserved structures such as pathogen-associated molecular patterns(PAMPs)and danger/damage associated molecular patterns(DAMPs).The most studied PRRs are Toll-like receptors(TLRs).Activation of TLRs triggers production of inflammatory cytokines and type I interferons(IFNs)via myeloid differentiation primary response gene 88(MyD88)-depen-dent or-independent signaling respectively,thereby modulating innate and adaptive immunity,as well as inflammatory responses.This review introduces the classification,structure,and specific ligands of TLRs,and focuses on their signal pathways and biological activities,as well as clinical relevance.These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases,including tuberculosis(TB),microbial keratitis,and hepatitis B and C.
基金supported by the Swiss National Science Foundation(grant number 200020_129935 and R’EQUIP 145023).
文摘E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewisx(sLex).Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode.Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLex and a glycomimetic antagonist thereof reveal an extended E-selectin conformation,which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations.Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution.This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment.The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists.This is of special interest,since their therapeutic potentialwas recently demonstrated with the pan-selectin antagonists GMI-1070(Rivipansel).
基金supported by the National Natural Science Foundation of China(Grant No.30801260).
文摘The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3(Tim-3)mRNA peripheral blood lymphocytes isolated from asthmaticin patients and to examine the correlation among Tim-3 mRNA,interleukin-4(IL-4),interferon-γ(IFN-γ)level,and FEV1/FVC(force expiratory volume in one second/forced vital capacity)to explore the role of Tim-3 in the development and progression of asthmatic inflammation.Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction(RT-PCR).The IL-4 and IFN-γlevels were determined by using enzyme-linked immunosorbent assay(ELISA).The correlation among Tim-3 mRNA,IL-4,IFN-γlevel,and pulmonary ventilatory capacity was analyzed.The expres-sion of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39�0.06,significantly higher than that in patients at the remission stage and controls(0.18�0.05 and 0.07�0.03,P<0.05).The level of IL-4 in patients with acute asthma exacerbation was 68.42�10.54,significantly higher than that in the patients at the remission stage and controls(41.83�9.37 and 32.75�8.16,P<0.05).The level of IL-4 in patients in remission was significantly higher than that in controls(P<0.05).The level of IFN-γin patients with acute asthma exacerbation was 65.74�7.85,significantly lower than that in patients in remission and the control group(120.84�11.62 and 139.65�13.47,P<0.05).The level of IFN-γin patients in asthma remission was significantly lower than that in controls(P<0.05).Tim-3 mRNA expression was positively correlated with the level of IL-4(r=0.68,P<0.05)and negatively with the level of IFN-γand pulmonary ventilatory capacity(r=–0.85,r=–0.76,both P<0.01).The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation.
基金supported by the Special Funds for Major State Basic Research Program of China(973 Program)(No.G2000056901).
文摘The role of high sensitivity C-reactive protein(hsCRP)in predicting prognosis after stroke in the Asian population has not been investigated.We hypothesized that elevated levels of hsCRP were associated with worsening prognosis after stroke in Chinese patients.Two hundred and ninety consecutive patients withfirst-onset stroke and 290 age-and gender-matched control subjects without any cerebrovascular disease were enrolled for study.Plasma hsCRP level was detected and subsequent vascular events and death were recorded in both groups over a 5-year period.Compared to control group,patients presenting with stroke had higher plasma hsCRP level(3.3±3.8 vs 1.3±2.2 mg/L,P<0.01).Furthermore,in the group of patients with stroke,the mean plasma hsCRP level was higher in patients who developed subsequent vascular diseases or died as compared with the patients without further complications(4.4±4.3 vs 2.7±3.3 mg/L,P<0.01).Compared to the lowest tertile of hsCRP level,the relative risk for vascular events or death in stroke patients was 2.91 in the highest tertile of hsCRP(95%CI,1.54–5.50,P=0.001).This increase in relative risk for vascular events or death in stroke patients continued after adjustment for age,sex and other cardiovascular risk factors such as hypertension and diabetes(OR:2.771,95%CI:1.367–5.617,P=0.005).Thesefindings indicate that increased hsCRP level is associated with worsening prognosis after stroke in Chinese patients and suggests that inflammation is correlated with stroke outcome.
