Autophagy facilitates IFN-δ-induced Jak2-STAT1 activation and cellular inflammation

Yu-Ping Chang, Cheng-Chieh Tsai, Wei-Ching Huang, Chi-Yun Wang, Chia-Ling Chen, Yee-Shin Lin, Jui-In Kai, Chia-Yuan Hsieh, Yi-Lin Cheng, Pui-Ching Choi, Shun-Hua Chen, Shih-Ping Chang, Hsiao-Sheng Liu, Chiou Feng Lin

研究成果: 雜誌貢獻文章

63 引文 斯高帕斯(Scopus)

摘要

Autophagy is regulated for IFN-γ-mediated antimicrobial efficacy; however, its molecular effects for IFN-γ signaling are largely unknown. Here, we show that autophagy facilitates IFN-γ-activated Jak2-STAT1. IFN-γ induces autophagy in wild-type but not in autophagy protein 5 (Atg5-/-)-deficient mouse embryonic fibroblasts (MEFs), and, autophagy-dependently, IFN-γ induces IFN regulatory factor 1 and cellular inflammatory responses. Pharmacologically inhibiting autophagy using 3-methyladenine, a known inhibitor of class III phosphatidylinositol 3-kinase, confirms these effects. Either Atg5-/- or Atg7-/- MEFs are, independent of changes in IFN-γ receptor expression, resistant to IFN-γ-activated Jak2-STAT1, which suggests that autophagy is important for IFN-γ signal transduction. Lentivirus-based short hairpin RNA for Atg5 knockdown confirmed the importance of autophagy for IFN-γ-activated STAT1. Without autophagy, reactive oxygen species increase and cause SHP2 (Src homology-2 domain-containing phosphatase 2)-regulated STAT1 inactivation. Inhibiting SHP2 reversed both cellular inflammation and the IFN-γ-induced activation of STAT1 in Atg5-/- MEFs. Our study provides evidence that there is a link between autophagy and both IFN-γ signaling and cellular inflammation and that autophagy, because it inhibits the expression of reactive oxygen species and SHP2, is pivotal for Jak2-STAT1 activation.
原文英語
頁(從 - 到)28715-28722
頁數8
期刊Journal of Biological Chemistry
285
發行號37
DOIs
出版狀態已發佈 - 九月 10 2010

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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    Chang, Y-P., Tsai, C-C., Huang, W-C., Wang, C-Y., Chen, C-L., Lin, Y-S., Kai, J-I., Hsieh, C-Y., Cheng, Y-L., Choi, P-C., Chen, S-H., Chang, S-P., Liu, H-S., & Lin, C. F. (2010). Autophagy facilitates IFN-δ-induced Jak2-STAT1 activation and cellular inflammation. Journal of Biological Chemistry, 285(37), 28715-28722. https://doi.org/10.1074/jbc.M110.133355