| OBJECTIVE: The aim of the present study was to determine the effects and potential mechanisms of IL-6 on ABCA1 and ABCG1 expression and cholesterol efflux in human macrophage foam cells.MEHTODS: In the present study, Human THP-1 cells pre-incubated oxLDL served as foam cell models. Specific mRNA was quantified by real-time PCR, protein expression by Western blotting. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content.RESULTS: IL-6 significantly decreased the expression of ABCA1 and ABCG1 and cholesterol efflux in the THP-1 macrophage-derived foam cells. Liver X receptorsα(LXRα) which can regulate the expression of ABCA1 and ABCG1 were also down-regulated by IL-6 treatment. IL-6 also suppressed the effects of T0901317 towards the expression of ABCA1 and ABCG1. LXRαsiRNA reversed the effect of IL-6 on ABCA1 and ABCG1. Meanwhile, IL-6 induces JAK/STAT3 activation in a dose- and time-dependent manner, which was inhibited by a JAK inhibitor piceastannol. Furthermore, treatment with piceastannol or STAT3 siRNA reversed the effect of IL-6 on LXRs, ABCA1 and ABCG1.CONCLUSION: IL-6 decreased ABCA1 and ABCG1 expression and inhibited cholesterol efflux, which was mediated by IL-6-induced JAK/STAT3 signaling pathway and accompanying LXRαinhibition.
|
PDF Full Text Request