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

33 引文 (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Yes

指紋

Interferon-alpha
Interferon alpha-beta Receptor
Melanoma
p38 Mitogen-Activated Protein Kinases
Cytokines
Phosphotransferases
Ubiquitination
Interleukin-1
Neoplasms
Cell Survival
Down-Regulation
Phosphorylation
Ligands
Inflammation
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

引用此文

Huangfu, W. C., Qian, J., Liu, C., Liu, J., Lokshin, A. E., Baker, D. P., ... Fuchs, S. Y. (2012). Inflammatory signaling compromises cell responses to interferon alpha. Oncogene, 31(2), 161-172. https://doi.org/10.1038/onc.2011.221

Inflammatory signaling compromises cell responses to interferon alpha. / Huangfu, W. C.; Qian, J.; Liu, C.; Liu, J.; Lokshin, A. E.; Baker, D. P.; Rui, H.; Fuchs, S. Y.

於: Oncogene, 卷 31, 編號 2, 12.01.2012, p. 161-172.

研究成果: 雜誌貢獻文章

Huangfu, WC, Qian, J, Liu, C, Liu, J, Lokshin, AE, Baker, DP, Rui, H & Fuchs, SY 2012, 'Inflammatory signaling compromises cell responses to interferon alpha', Oncogene, 卷 31, 編號 2, 頁 161-172. https://doi.org/10.1038/onc.2011.221
Huangfu WC, Qian J, Liu C, Liu J, Lokshin AE, Baker DP 等. Inflammatory signaling compromises cell responses to interferon alpha. Oncogene. 2012 1月 12;31(2):161-172. https://doi.org/10.1038/onc.2011.221
Huangfu, W. C. ; Qian, J. ; Liu, C. ; Liu, J. ; Lokshin, A. E. ; Baker, D. P. ; Rui, H. ; Fuchs, S. Y. / Inflammatory signaling compromises cell responses to interferon alpha. 於: Oncogene. 2012 ; 卷 31, 編號 2. 頁 161-172.
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