Open AccessA novel TLR 2‐triggered signalling crosstalk synergistically intensifies TNF ‐mediated IL ‐6 induction
Author(s) -
Chang YuLing,
Chen TzuHui,
Wu YiHsiu,
Chen GuannAn,
Weng TzuHuei,
Tseng PingHui,
Hsieh ShieLiang,
Fu ShuLing,
Lin ChiHung,
Chen ChunJen,
Chu ChingLiang,
Chio Iok In Christine,
Mak Tak Wah,
Chen NienJung
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12294
Subject(s) - crosstalk , tumor necrosis factor alpha , receptor , inflammation , microbiology and biotechnology , cytokine , signal transducing adaptor protein , signal transduction , toll like receptor , immunology , biology , innate immune system , immune system , biochemistry , physics , optics
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 TLR 2‐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 ( TRAF 6) and TNFR ‐associated death domain, leading to a distinctive K63‐ubiquitinylated TRAF 6 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.