A novel TLR2‐triggered signalling crosstalk synergistically intensifies TNF‐mediated IL‐6 induction. Issue 7 (24th April 2014)

• Record Type: Journal Article
• Authors: Chang, Yu‐Ling; Chen, Tzu‐Hui; Wu, Yi‐Hsiu; Chen, Guann‐An; Weng, Tzu‐Huei; Tseng, Ping‐Hui; Hsieh, Shie‐Liang; Fu, Shu‐Ling; Lin, Chi‐Hung; Chen, Chun‐Jen; Chu, Ching‐Liang; Chio, Iok In Christine; Mak, Tak Wah; Chen, Nien‐Jung
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 7(2014)
• Page Start: 1344
• Page End: 1357
• Publication Date: 2014-04-24
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12294
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12294-abs-0001"> <title>Abstract</title> <p>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.</p> </abstract>