Inflammatory signaling compromises cell responses to interferon alpha.
Inflammatory signaling compromises cell responses to interferon alpha.
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DOI：
10.1038/onc.2011.221
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发表时间：
2012-01-12
期刊：
影响因子：
8
通讯作者：
Fuchs, S. Y.
中科院分区：
文献类型：
--
作者：
HuangFu, W-C;Qian, J.;Liu, C.;Liu, J.;Lokshin, A. E.;Baker, D. P.;Rui, H.;Fuchs, S. Y.
干扰素α（IFNα）广泛用于治疗黑色素瘤和某些其它恶性肿瘤。这种细胞因子以及相关的IFNβ发挥有效的抗肿瘤作用;然而，它们在患者中的疗效通常是次优的。在这里，我们报告说，炎症信号阻碍IFNα/β的影响。黑色素瘤细胞可以分泌促炎细胞因子，其通过激活I型IFN受体的IFNAR 1链的磷酸化和随后的泛素化和加速降解的配体非依赖性途径来抑制对IFNα/β的细胞应答。p38蛋白激酶的催化活性是IFNAR 1下调和抑制由促炎细胞因子如白细胞介素1（IL-1）诱导的IFNα/β信号传导所必需的。在临床黑素瘤标本中，p38激酶的激活与IFNAR 1的蛋白水平呈负相关。抑制p38激酶增强了IFNα/β对体外和体内细胞活力和生长的抑制作用。本文还讨论了炎症和p38蛋白激酶在调节正常和肿瘤细胞对IFNα/β反应中的作用。
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 role of inflammation and p38 protein kinase in regulating cellular responses to IFNα/β in normal and tumor cells are discussed.
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影响因子：
7.8
作者：
Kumar, K. G. Suresh;Barriere, Herve;Carbone, Christopher J.;Liu, Jianghuai;Swaminathan, Gayathri;Xu, Ping;Li, Ying;Baker, Darren P.;Peng, Junmin;Lukacs, Gergely L.;Fuchs, Serge Y.
通讯作者：
Fuchs, Serge Y.
DOI：
10.1007/978-0-387-77574-6_8
发表时间：
2008-01-01
期刊：
SUNLIGHT, VITAMIN D AND SKIN CANCER
影响因子：
--
作者：
Leiter, Ulrike;Garbe, Claus
通讯作者：
Garbe, Claus
影响因子：
4.3
作者：
Hui, Lijian;Bakiri, Latifa;Wagner, Erwin F.
通讯作者：
Wagner, Erwin F.
影响因子：
2
作者：
Linkov, Faina;Ferris, Robert L.;Yurkovetsky, Zoya;Marrangoni, Adele;Velikokhatnaya, Lyudmila;Gooding, William;Nolan, Brian;Winans, Matthew;Siegel, Eric R.;Lokshin, Anna;Stack, Brendan C., Jr.
通讯作者：
Stack, Brendan C., Jr.
影响因子：
6.7
作者：
Balkwill, F.;Mantovani, A.
通讯作者：
Mantovani, A.