202: IL-6 Inhibited starvation-induced autophagy through STAT3/Bcl2/Beclin1 pathway

Abstract

Autophagy is widely existed as a lysosome-dependent degradative way in eukaryotic cells. Under normal conditions, autophagy is in the basal state, but in abnormal cases autophagy is then activated such as starvation, metabolic pressure, cyto-organelle damage and microbial infection. Some researches about the relationship between cytokines and autophagy have also received much more attention. IL-6, a pleiotropic cytokine secreted by many immune and immuno-related cells, can regulate cellular immunity and participate in the pathogenesis of some diseases. The main signal-transduction pathways downstream of IL-6/IL-6Rα/gp130 included JAK/STAT, PI3K/Akt and Ras/Erk pathway. These pathways also play an important role in the process of autophagy. Some investigators have also confirmed the effect of IL6 on autophagy. However these reports are controversial. Our results showed that the addition of IL-6 reduced the protein levels of LC3 and significantly activated the phosphorylation of STAT3 at Tyr705. Meantime the expression of Beclin1, a component of class III PI3K compex, was attenuated in U937 cells. Knockdown of Beclin1 by siRNA revealed its involvement in inhibition of autophagy by IL-6. STAT3 inhibitor LLL12 and the mutant STAT3Y705F suppressed the its phosphorylation and expression of Bcl-2 while enhanced expression of autophagy related proteins like LC3 and Beclin1. In conclusion, we proposed that p-STAT3 could mediate the inhibition of starvation-induced autophagy by exogenous IL-6. IL-6 could inhibit starvation-induced autophagy by STAT3/Bcl2/Beclin1 pathway in cells.