期刊
CYTOKINE & GROWTH FACTOR REVIEWS
卷 26, 期 5, 页码 475-487出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cytogfr.2015.07.004
关键词
Cytokine; Receptor; Trans-signaling; Inflammation; Signal transduction
资金
- German Federal Ministry of Education and Research (BMBF): E:Bio-Modul II InTraSig
- German Federal Ministry of Education and Research (BMBF): E:Bio-Modul I JAK-Sys
- Deutsche Forschungsgemeinschaft [SCHA 785/8-1]
- Deutsche Forschungsgemeinschaft Bonn, Germany [SFB841, C3, SFB877, A1]
Interleukin-6 (IL-6) is one of the most important inflammatory cytokines. IL-6 is unique in signaling via a membrane bound and a soluble receptor. Intriguingly, these two pathways strongly differ in their biologic consequences. While classic IL-6 signaling via the membrane bound receptor is mainly regenerative and protective, IL-6 trans-signaling via the soluble IL-6R is rather pro-inflammatory. Intracellular signaling of IL-6 in response to receptor activation is through STAT-dependent and STAT-independent signaling modules, which are regulated by a complex regulatory network. The complex biology of IL-6 has consequences for therapeutic targeting of this cytokine. We hypothesize that specific inhibition of the trans-signaling pathway may be superior to global blockade of IL-6 activity with help of antibodies directed against IL-6 or IL-6R. (C) 2015 Elsevier Ltd. All rights reserved.
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