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Keratin 8 limits TLR-triggered inflammatory responses through inhibiting TRAF6 polyubiquitination.
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.
Afiliación
  • Dong XM; Tianjin University, School of Chemical Engineering and Technology, Department of pharmaceutical engineering, Tianjin 300072, China.
  • Liu ED; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Meng YX; AnHui Medical University, Hefei, 230032, China.
  • Liu C; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, China.
  • Bi YL; AnHui Medical University, Hefei, 230032, China.
  • Wu HW; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, China.
  • Jin YC; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 1 Shuai Fu Yuan Hu Tong, Beijing 100730, China.
  • Yao JH; Tianjin University, School of Chemical Engineering and Technology, Department of pharmaceutical engineering, Tianjin 300072, China.
  • Tang LJ; AnHui Medical University, Hefei, 230032, China.
  • Wang J; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Li M; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Zhang C; AnHui Medical University, Hefei, 230032, China.
  • Yu M; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Zhan YQ; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Chen H; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Ge CH; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Yang XM; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
  • Li CY; Tianjin University, School of Chemical Engineering and Technology, Department of pharmaceutical engineering, Tianjin 300072, China.
Sci Rep ; 6: 32710, 2016 09 02.
Article en En | MEDLINE | ID: mdl-27586056
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Choque Séptico / Factor 6 Asociado a Receptor de TNF / Receptores Toll-Like / Queratina-8 / Ubiquitinación / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Choque Séptico / Factor 6 Asociado a Receptor de TNF / Receptores Toll-Like / Queratina-8 / Ubiquitinación / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido