Interleukin-5 Up-regulated ABCA1 Expression Though JAK2/STAT3 Pathways In THP-1 Macrophages

Objective: It had been reported that interleukin-5(IL-5) possessed the characteristic of atheroprotection, but the mechanism was still not fully understood. This study was aimed to investigate whether IL-5 up-regulates ATP-binding cassette transporter A1(ABCA1) through JAK2/STAT3 pathway in THP-1 macrophages.Methods: ABCA1 expression was detected after treated with IL-5 at different concentrations or incubated with IL-5(0.15 ng/ml) for different time(0, 6, 12, 24, 48 h) in THP-1 macrophages. Oil Red O staining was performed to observe the cellular lipid droplets. High performance liquid chromatography was used to evaluate the intracellular cholesterol content. Cholesterol efflux detetion was performed by liquid scintillator. ABCA1 mRNA was determined by RT-PCR. Western blot was used to determine ABCA1, JAK2(p-JAK2) and STAT3(p-STAT3) protein. IL-5 or anti-IL-5 antibody was used to treat cells for 24 h, p-JAK2 and p-STAT3 were examined. JAK2 and STAT3 inhibitor or corresponding selective small interfering RNA were also used to incubate together with IL-5, the levels of p-JAK2, p-STAT3 and ABCA1 were examined.Results: IL-5 significantly up-regulated the expression of ABCA1 protein and m RNA levels in both concentration- and time-dependent manners. IL-5 treatment also increased cholesterol efflux, and decreased cellular cholesterol. Both JAK2 and STAT3 were activated sequentially in response to IL-5 treatment. Importantly, inhibition of JAK2 or STAT3 by selective inhibitor or corresponding small interfering RNA completely inhibited the stimulatory effects of IL-5.Conclusions: Our results have revealed that IL-5 induces ABCA1 expression and promotes cholesterol efflux likely through the JAK2/STAT3 signaling pathway.