ABSTRACT
Objective To explore the influence of apoptosis-associated speck-like protein containing a caspase recruitment do-main(ASC)and Caspase-1 on the pathogenesis of primary biliary cirrhosis(PBC).Methods The real-time PCR,Western blot,py-rophosphate sequencing and ELISA were adopted to respectively detect the relative expressions of mRNA and protein of peripheral blood mononuclear cells(PBMS)Caspase-1 and ASC as well as the methylation status of ASC promoter region and plasma Caspase-1 and IL-18 expression levels in 30 cases of PBC and healthy controls.Results The mRNA and protein expressions of PBMC Caspase-1 and ASC in the PBC group were significantly higher than those in the control group(P<0.05).The methylation rate of ASC promoter Island1(ISI)was significantly lower than that of the control group(P<0.05),which of Island 2(IS2)was smaller than the background value and had no methylation occurrence.The levels of plasma Caspase-1 and IL-18 in the PBC group were sig-nificantly higher than those in the control group(P<0.05).The ASC mRNA in the PBC group was significantly correlated with the Caspase-1 mRNA expression(P<0.05);the methylation rates at loci 1,2,4,5 of ASC promoter region CpG island were nega-tively correlated with ASC mRNA expression(P< 0.05),and which at loci 3,6 had no correlation with their expressions(P>0.05);plasma Caspase-1 and IL-18 levels showed the obviously positive correlation.Conclusion ASC and Caspase-1 are involved in the immune inflammatory response in PBC.
ABSTRACT
Objective To explore the correlation between NF-κB signaling pathways activated by IL-18 in CD4+ T cells and the pathogenesis of PBC.Methods We detected the expression of IL-18 mRNA in PBMCs,IL-18 level in plasma,receptor IL-18R on surface of CD4+ T cell,proliferation rate of CD4+T cell and its NF-κB signaling pathway protein IκBα and NF-κB p65 by qRT-PCR,ELISA,flow cytometry,MACS and Western blot on 32 cases of patients with PBC (PBC group) and 32 healthy people (control group) in Guizhou provincial people′s hospital.Results The level of IL-18 in PBC group was significantly higher than that in control group (P<0.05).The relative expression of IL-18 mRNA in PBC group was significantly higher than that in control group (P<0.05).The percentage of CD4+T cells expressing IL-18Rα in PBC group was higher than that in control group (P<0.05).The proliferation rate of CD4+T cells stimulated by IL-18 in PBC group was significantly higher than that in healthy control group (P<0.01).The relative expression levels of NF-κB p65 protein were up-regulated in IL-18,and the expression of IκBα protein in each group was significantly increased,especially in PBC group (P<0.01).Conclusion IL-18 can activate NF-κB signal pathway in CD4+ T cells and participate in the pathogenesis of primary biliary cirrhosis.