A novel TLR2‐triggered signalling crosstalk synergistically intensifies TNF‐mediated IL‐6 induction

Journal of Cellular and Molecular Medicine

Yu-Ling Chang⁵  Tzu-Hui Chen⁵  Yi-Hsiu Wu⁵  Guann-An Chen⁵  Tzu-Huei Weng⁵  Ping-Hui Tseng⁴  Shie-Liang Hsieh⁵  Shu-Ling Fu²  Chi-Hung Lin⁵  Chun-Jen Chen³  Ching-Liang Chu¹  Iok In Christine Chio⁶  Tak Wah Mak⁶ 

[1] Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan;Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan;Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan;Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan;The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

关键词: Toll‐like receptor;    tumour necrosis factor;    signalling crosstalk;    TRAF6;    TRADD;   

DOI  :  10.1111/jcmm.12294

来源: Wiley

【 摘 要 】

Abstract

Toll-like receptors (TLR) recognize pathogens and trigger the production of vigorous pro-inflammatory cytokines [such as tumour necrosis factor (TNF)] that induce systemic damages associated with sepsis and chronic inflammation. Cooperation between signals of TLR and TNF receptor has been demonstrated through the participation of TNF receptor 1 (TNFR) adaptors in endotoxin tolerance. Here, we identify a TLR2-mediated synergy, through a MyD88-independent crosstalk, which enhances subsequent TNF-mediated nuclear factor-kappa B activation and interleukin-6 induction. Membrane-associated adaptor MAL conduces the link between TNF receptor-associated factor 6 (TRAF6) and TNFR-associated death domain, leading to a distinctive K63-ubiquitinylated TRAF6 recruitment into TNFR complex. In summary, our results reveal a novel route of TLR signal that synergistically amplifies TNF-mediated responses, indicating an innovative target for inflammation manipulation.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.