| Literature DB >> 29230038 |
Meng Du1,2, Lin Yuan1,2, Xin Tan1,2, Dandan Huang1,2, Xiaojing Wang3, Zhe Zheng1,2, Xiaoxiang Mao1,2, Xiangrao Li1,2, Liu Yang1,2, Kun Huang1,2, Fengxiao Zhang1,2, Yan Wang1,2, Xi Luo1,2, Dan Huang1,2, Kai Huang4,5.
Abstract
Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRR) with a crucial function in innate immune responses. Activation of TLR4 signaling at the plasma membrane by lipopolysaccharide (LPS) stimulates proinflammatory signaling pathways dependent on the E3 ubiquitin ligase TRAF6. Here we show the LPS-induced long non-coding RNA (lncRNA) Mirt2 functions as a checkpoint to prevent aberrant activation of inflammation, and is a potential regulator of macrophage polarization. Mirt2 associates with, and attenuates Lys63 (K63)-linked ubiquitination of, TRAF6, thus inhibiting activation of NF-κB and MAPK pathways and limiting production of proinflammatory cytokines. Adenovirus mediated gene transfer of Mirt2 protects mice from endotoxemia induced fatality and multi-organ dysfunction. These findings identify lncRNA Mirt2 as a negative feedback regulator of excessive inflammation.Entities:
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Year: 2017 PMID： 29230038 PMCID： PMC5725456 DOI： 10.1038/s41467-017-02229-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919