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Keratin 8 limits TLR-triggered inflammatory responses through inhibiting TRAF6 polyubiquitination

Toll-like receptors (TLRs) have critical roles in innate immunity and inflammation and the detailed mechanisms by which TLR signaling is fine tuned remain unclear. Keratin 8 (CK8) belongs to the type II keratin family and is the major compontent of the intermediate filaments of simple or single-laye...

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Detalles Bibliográficos
Autores principales: Dong, Xiao-Ming, Liu, En-Dong, Meng, Yun-Xiao, Liu, Chao, Bi, Ya-Lan, Wu, Huan-Wen, Jin, Yan-Chao, Yao, Jing-Hui, Tang, Liu-Jun, Wang, Jian, Li, Min, Zhang, Chao, Yu, Miao, Zhan, Yi-Qun, Chen, Hui, Ge, Chang-Hui, Yang, Xiao-Ming, Li, Chang-Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009362/
https://www.ncbi.nlm.nih.gov/pubmed/27586056
http://dx.doi.org/10.1038/srep32710
Descripción
Sumario:Toll-like receptors (TLRs) have critical roles in innate immunity and inflammation and the detailed mechanisms by which TLR signaling is fine tuned remain unclear. Keratin 8 (CK8) belongs to the type II keratin family and is the major compontent of the intermediate filaments of simple or single-layered epithelia. Here we report that down-regulation of CK8 in mice enhanced TLR-mediated responses, rendering mice more susceptible to lipopolysaccharide (LPS)-induced endotoxin shock and Escherichia coli–caused septic peritonitis with reduced survival, elevated levels of inflammation cytokines and more severe tissue damage. We found that CK8 suppressed TLR-induced nuclear factor (NF)-κB activation and interacted with the adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) to prevent its polyubiquitination. Our findings demonstrate a novel role of CK8 in negative regulation of TLR/NF-κB signaling and highlight a previously unidentified nonclassical function for CK8 in limiting inflammatory responses.