Inflammatory signaling compromises cell responses to interferon alpha

W. C. Huangfu, J. Qian, C. Liu, J. Liu, A. E. Lokshin, D. P. Baker, H. Rui, S. Y. Fuchs

研究成果: 雜誌貢獻文章同行評審

45 引文 斯高帕斯(Scopus)

摘要

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNΒ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/Β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/Β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/Β signaling induced by proinflammatory cytokines such as interleukin 1 (IL-1). Activation of p38 kinase inversely correlated with protein levels of IFNAR1 in clinical melanoma specimens. Inhibition of p38 kinase augmented the inhibitory effects of IFNα/Β on cell viability and growth in vitro and in vivo. The roles of inflammation and p38 protein kinase in regulating cellular responses to IFNα/Β in normal and tumor cells are discussed.
原文英語
頁(從 - 到)161-172
頁數12
期刊Oncogene
31
發行號2
DOIs
出版狀態已發佈 - 一月 12 2012
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 癌症研究

指紋

深入研究「Inflammatory signaling compromises cell responses to interferon alpha」主題。共同形成了獨特的指紋。

引用此