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A rapid administration of GW 4064 inhibits the NLRP 3 inflammasome activation independent of farnesoid X receptor agonism
Author(s) -
Xie Shujun,
Guo Chuansheng,
Chi Zhexu,
Huang Bo,
Wu Yihua,
Wang Di,
Xia Dajing
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12782
Subject(s) - farnesoid x receptor , inflammasome , receptor , microbiology and biotechnology , chemistry , nuclear receptor , biology , biochemistry , gene , transcription factor
GW 4064 is a small molecule known to be an agonist of the nuclear farnesoid X receptor ( FXR ). We found that GW 4064 inhibits the NLR family CARD domain containing 3 ( NLRP 3) inflammasome activation in an FXR ‐independent manner as evidenced by its similar inhibitory effect on NLRP 3 inflammasome activation in FXR ‐deficient macrophages. Interestingly, GW 4064 decreases the nigericin‐induced oligomerization and ubiquitination of ASC which is critical for the NLRP 3 inflammasome activation. In vivo results indicate that GW 4064 could partially rescue the symptoms of NLRP 3‐dependent inflammatory disease models. These results not only necessitate cautious interpretation of the biological function of GW 4064 as an FXR agonist, but also provide a potential therapeutic approach using GW 4064 in the treatment of NLRP 3‐related diseases.