Inflammatory signaling compromises cell responses to interferon alpha
| Autor: | Serge Y. Fuchs, Hallgeir Rui, Darren P. Baker, Wei-Chun HuangFu, Anna Lokshin, Chengbao Liu, Juan Qian, Jianghuai Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
p38 mitogen-activated protein kinases medicine.medical_treatment receptor Alpha interferon Mice SCID Biology p38 Mitogen-Activated Protein Kinases Article Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Interferon Cell Line Tumor ubiquitin Genetics medicine melanoma cancer Animals Humans Protein kinase A Molecular Biology 030304 developmental biology Inflammation 0303 health sciences Interferon-alpha interferon 3. Good health Cytokine 030220 oncology & carcinogenesis Cancer research Cytokines Signal transduction Inflammation Mediators medicine.drug Signal Transduction |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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