In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on...In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on platelets as the rhodocytin receptor.Thereafter,several studies have showed that platelet CLEC-2 isinvolved in lymphatic/blood vessel separation,tumormetastasis and thrombus formation.展开更多
Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary ...Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary artery disease(CAD).A total of 216 patients,including 14 cases of stable angina pectoris(SAP,non-ACS)and 202 cases of acute coronary syndrome(ACS),and 89 non-CAD control subjects were enrolled.Plasma levels of soluble CLEC-2(sCLEC-2)were measured using the enzyme-linked immunosorbent assay(ELISA).Compared with the control group(65.69(55.36–143.22)pg/mL),the plasma levels of sCLEC-2 were significantly increased in patients with CAD(133.67(88.76–220.09)pg/mL)and ACS(134.16(88.88–225.81)pg/mL).The multivariate adjusted odds ratios(95%confidence interval)of CAD reached 2.01(1.52–2.66)(Ptrend<0.001)for each 1-quartile increase in sCLEC-2.Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence(Plinearity<0.001).The addition of sCLEC-2 to conventional risk factors improved the C statistic(0.821 vs.0.761,P=0.004)and reclassification ability(net reclassification improvement:57.45%,P<0.001;integrated discrimination improvement:8.27%,P<0.001)for CAD.In conclusion,high plasma sCLEC-2 is independently associated with CAD risk,and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.展开更多
AIM: To investigate the co-regulation of dendritic cell- associated C-type lectin-1 (Dectin-1), Toll-like receptor 2 (TLR2), and relative chemotactic factors in the Telomease- immortalized human corneal epitheli...AIM: To investigate the co-regulation of dendritic cell- associated C-type lectin-1 (Dectin-1), Toll-like receptor 2 (TLR2), and relative chemotactic factors in the Telomease- immortalized human corneal epithelial (THCE) cells after exposure to ,Aspergillus fumigatus (Af) hyphae. METHODS: The normal THCE cells were investigated as control. After cultured in vitro with Af hyphae, with or without laminarin and anti-TLR2 antibody for 4, 8, 16 and 24h, THCE cells were harvested. The expression of Dectin-1, TLR2, CXCL1 and CXCL8 mRNA were measured by real-time quantitative polymerase chain reaction at the stimulation of 4, 8 and 16h separately. The protein expression of Dectin-1 and TLR2 were analyzed at 8, 16, and 24h by Western blot. ~ RESULTS: The mRNA CXCL8 increased in THCE expression of CXCL1 and cells after stimulated by Af hyphae. The stimulatory effects on these inflammatory chemokines were shown in a dose-dependent manner and reached the peak at 8h. Af hyphae significantly stimulated the production of Dectin-1 and TLR2 in THCE cells at both mRNA and protein levels. The protein of Dectin-1 and TLR2 gradually increased till 16h. While pretreated with laminarin (a Dectin-1 inhibitor), the expression of TLR2, CXCL1 and CXCL8 all decreased dramatically at the peak point, interestingly, when pretreated with TLR2 neutralizing antibody, the expression of Dectin -1, CXCL1 and CXCL8 also decreased dramatically at the peak point. CONCLUSION: These findings suggest that Dectin-1 and TLR2 co-regulated with each other after treated with inactive Af hyphae in the THCE cells, and they contribute together to the inflammatory responses by induction of chemokines CXCL1 and CXCL8.展开更多
Background:The C-type lectin receptor(CLR)expressed by DCs participates in the recognition and capture of various glycosylated self-antigens and pathogens.Understanding the diversity of the CLR expressed by DCs,as wel...Background:The C-type lectin receptor(CLR)expressed by DCs participates in the recognition and capture of various glycosylated self-antigens and pathogens.Understanding the diversity of the CLR expressed by DCs,as well as their role in maintaining the balance between Th1-type and Th2-type cytokines would promote the understanding of the pathogenesis of many diseases including preeclampsia(PE).Methods:DCs were isolated from the placentae of healthy women who underwent normal pregnancies and infected with a CLR lentiviral(LV)vector for gene overexpression or small interfering RNA(siRNA)knockdown.DCs were cocultured with T-cells and EVCTs,and five groups were established as follows:Group 1-DCs from healthy women who underwent normal pregnancies,Group 2-DCs from women with preeclampsia(PE),Group 3-DCs infected with empty LV vectors,Group 4-DCs infected with a CLR LV vector for gene overexpression,and Group 5-DCs infected with a CLR LV vector for siRNA knockdown.The levels of Th1-and Th2-type cytokines were measured in all groups.Results:The levels of Th1-type cytokines were significantly higher in women with PE than in those with normal pregnancies(P<0.05).Among these five groups,the Th1/Th2 ratio of Group 5 was highest(P<0.05).There was no difference in the Th1/Th2 ratio between Groups 1 and 3.Conclusions:There was a Th1/Th2 imbalance in women with PE displaying Th1-type immunity.CLR-overexpressing DCs showed a diminished capacity to polarize na?ve T-cells into Th1 effector cells.The impaired Th1 response in DCs was rescued by CLR siRNA knockdown.In conclusion,DCs may affect the production of cytokines and the migration of T-cells through CLR-mediated signaling pathways during pregnancy.展开更多
文摘In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on platelets as the rhodocytin receptor.Thereafter,several studies have showed that platelet CLEC-2 isinvolved in lymphatic/blood vessel separation,tumormetastasis and thrombus formation.
基金supported by grants from the National Natural Science Foundation of China(Nos.81870325,81620108001,and 91739302 to Li Zhu)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China and Suzhou Key laboratory of Thrombosis and Vascular Diseases(to Li Zhu)+1 种基金the Suzhou Science and Technology Project Foundation(No.SYS201721 to Li Xiang)the Young Investigator Pre-research Foundation of the Second Affiliated Hospital of Soochow University(No.SDFEYQN1717 to Tao You).
文摘Accumulating evidence suggests that C-type lectin-like receptor-2(CLEC-2)plays an important role in atherothrombosis.In this case-control study,we investigated the association between CLEC-2 and incidence of coronary artery disease(CAD).A total of 216 patients,including 14 cases of stable angina pectoris(SAP,non-ACS)and 202 cases of acute coronary syndrome(ACS),and 89 non-CAD control subjects were enrolled.Plasma levels of soluble CLEC-2(sCLEC-2)were measured using the enzyme-linked immunosorbent assay(ELISA).Compared with the control group(65.69(55.36–143.22)pg/mL),the plasma levels of sCLEC-2 were significantly increased in patients with CAD(133.67(88.76–220.09)pg/mL)and ACS(134.16(88.88–225.81)pg/mL).The multivariate adjusted odds ratios(95%confidence interval)of CAD reached 2.01(1.52–2.66)(Ptrend<0.001)for each 1-quartile increase in sCLEC-2.Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence(Plinearity<0.001).The addition of sCLEC-2 to conventional risk factors improved the C statistic(0.821 vs.0.761,P=0.004)and reclassification ability(net reclassification improvement:57.45%,P<0.001;integrated discrimination improvement:8.27%,P<0.001)for CAD.In conclusion,high plasma sCLEC-2 is independently associated with CAD risk,and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.
基金Supported by the National Scientific Foundation of China (No. 81170825)
文摘AIM: To investigate the co-regulation of dendritic cell- associated C-type lectin-1 (Dectin-1), Toll-like receptor 2 (TLR2), and relative chemotactic factors in the Telomease- immortalized human corneal epithelial (THCE) cells after exposure to ,Aspergillus fumigatus (Af) hyphae. METHODS: The normal THCE cells were investigated as control. After cultured in vitro with Af hyphae, with or without laminarin and anti-TLR2 antibody for 4, 8, 16 and 24h, THCE cells were harvested. The expression of Dectin-1, TLR2, CXCL1 and CXCL8 mRNA were measured by real-time quantitative polymerase chain reaction at the stimulation of 4, 8 and 16h separately. The protein expression of Dectin-1 and TLR2 were analyzed at 8, 16, and 24h by Western blot. ~ RESULTS: The mRNA CXCL8 increased in THCE expression of CXCL1 and cells after stimulated by Af hyphae. The stimulatory effects on these inflammatory chemokines were shown in a dose-dependent manner and reached the peak at 8h. Af hyphae significantly stimulated the production of Dectin-1 and TLR2 in THCE cells at both mRNA and protein levels. The protein of Dectin-1 and TLR2 gradually increased till 16h. While pretreated with laminarin (a Dectin-1 inhibitor), the expression of TLR2, CXCL1 and CXCL8 all decreased dramatically at the peak point, interestingly, when pretreated with TLR2 neutralizing antibody, the expression of Dectin -1, CXCL1 and CXCL8 also decreased dramatically at the peak point. CONCLUSION: These findings suggest that Dectin-1 and TLR2 co-regulated with each other after treated with inactive Af hyphae in the THCE cells, and they contribute together to the inflammatory responses by induction of chemokines CXCL1 and CXCL8.
基金This study was supported by the National Natural Science Foundation of China(81200477).
文摘Background:The C-type lectin receptor(CLR)expressed by DCs participates in the recognition and capture of various glycosylated self-antigens and pathogens.Understanding the diversity of the CLR expressed by DCs,as well as their role in maintaining the balance between Th1-type and Th2-type cytokines would promote the understanding of the pathogenesis of many diseases including preeclampsia(PE).Methods:DCs were isolated from the placentae of healthy women who underwent normal pregnancies and infected with a CLR lentiviral(LV)vector for gene overexpression or small interfering RNA(siRNA)knockdown.DCs were cocultured with T-cells and EVCTs,and five groups were established as follows:Group 1-DCs from healthy women who underwent normal pregnancies,Group 2-DCs from women with preeclampsia(PE),Group 3-DCs infected with empty LV vectors,Group 4-DCs infected with a CLR LV vector for gene overexpression,and Group 5-DCs infected with a CLR LV vector for siRNA knockdown.The levels of Th1-and Th2-type cytokines were measured in all groups.Results:The levels of Th1-type cytokines were significantly higher in women with PE than in those with normal pregnancies(P<0.05).Among these five groups,the Th1/Th2 ratio of Group 5 was highest(P<0.05).There was no difference in the Th1/Th2 ratio between Groups 1 and 3.Conclusions:There was a Th1/Th2 imbalance in women with PE displaying Th1-type immunity.CLR-overexpressing DCs showed a diminished capacity to polarize na?ve T-cells into Th1 effector cells.The impaired Th1 response in DCs was rescued by CLR siRNA knockdown.In conclusion,DCs may affect the production of cytokines and the migration of T-cells through CLR-mediated signaling pathways during pregnancy.