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

Yu Ling Chang; Tzu Hui Chen; Yi Hsiu Wu; Guann An Chen; Tzu Huei Weng; Ping Hui Tseng; Shie Liang Hsieh; Shu Ling Fu; Chi Hung Lin; Chun Jen Chen; Ching Liang Chu; Iok In Christine Chio; Tak Wah Mak; Nien Jung Chen

doi:10.1111/jcmm.12294

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

Yu Ling Chang, Tzu Hui Chen, Yi Hsiu Wu, Guann An Chen, Tzu Huei Weng, Ping Hui Tseng, Shie Liang Hsieh, Shu Ling Fu, Chi Hung Lin, Chun Jen Chen, Ching Liang Chu, Iok In Christine Chio, Tak Wah Mak, Nien Jung Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	1344-1357
Number of pages	14
Journal	Journal of Cellular and Molecular Medicine
Volume	18
Issue number	7
DOIs	https://doi.org/10.1111/jcmm.12294
State	Published - Jul 2014

Keywords

Signalling crosstalk
TRADD
TRAF6
Toll-like receptor
Tumour necrosis factor

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10.1111/jcmm.12294

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Chang, Y. L., Chen, T. H., Wu, Y. H., Chen, G. A., Weng, T. H., Tseng, P. H., Hsieh, S. L., Fu, S. L., Lin, C. H., Chen, C. J., Chu, C. L., Chio, I. I. C., Mak, T. W., & Chen, N. J. (2014). A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction. Journal of Cellular and Molecular Medicine, 18(7), 1344-1357. https://doi.org/10.1111/jcmm.12294

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title = "A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction",

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.",

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author = "Chang, {Yu Ling} and Chen, {Tzu Hui} and Wu, {Yi Hsiu} and Chen, {Guann An} and Weng, {Tzu Huei} and Tseng, {Ping Hui} and Hsieh, {Shie Liang} and Fu, {Shu Ling} and Lin, {Chi Hung} and Chen, {Chun Jen} and Chu, {Ching Liang} and Chio, {Iok In Christine} and Mak, {Tak Wah} and Chen, {Nien Jung}",

year = "2014",

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doi = "10.1111/jcmm.12294",

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AU - Tseng, Ping Hui

AU - Hsieh, Shie Liang

AU - Fu, Shu Ling

AU - Lin, Chi Hung

AU - Chen, Chun Jen

AU - Chu, Ching Liang

AU - Chio, Iok In Christine

AU - Mak, Tak Wah

AU - Chen, Nien Jung

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AB - 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.

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

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Keywords

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