title: IL-6 Inhibits Starvation-induced Autophagy via the STAT3/Bcl-2 Signaling Pathway.
abstract: IL-6, a pleiotropic cytokine, has been investigated for its role in regulating autophagy. Yet, its mechanism of action remains unclear. Here, we show that IL-6 exerted anti-autophagic effects on U937 cells through the STAT3 signaling pathway in vitro. The addition of IL-6 to starved U937 cells significantly activated the phosphorylation level of STAT3 (p-STAT3) at Tyr705 and reduced the protein levels of microtubule-associated protein 1 light chain 3 of type II (LC3-II) and Beclin 1. By immunoblotting, we also observed a positive correlation between the p-STAT3 level and Bcl-2 level. Furthermore, treatment with a STAT3 inhibitor, LLL12, or overexpression of a mutant form, STAT3Y705F, reversed the inhibitory effect of IL-6 on autophagy. Knockdown of Beclin 1 or Atg14 by siRNA and over-expression of Beclin 1 indicated the involvement of class III PI3K complex in IL-6-mediated inhibition of autophagy. Taken together, these data indicate that IL-6 inhibits starvation-induced autophagy and that p-STAT3 mediates the signal transduction from IL-6 to downstream proteins including Bcl-2 and Beclin1.
authors.affiliation: The National Education Base for Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, PR China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Qin
authors.affiliation: The National Education Base for Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, PR China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The National Education Base for Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, PR China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: He
authors.affiliation: The National Education Base for Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, PR China.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Yan
authors.affiliation: The National Education Base for Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, PR China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D001343:Autophagy; D000071186:Beclin-1; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D013217:Starvation
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015850:Interleukin-6; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases