Open AccessTranilast directly targets NLRP 3 to treat inflammasome‐driven diseases
Author(s) -
Huang Yi,
Jiang Hua,
Chen Yun,
Wang Xiaqiong,
Yang Yanqing,
Tao Jinhui,
Deng Xianming,
Liang Gaolin,
Zhang Huafeng,
Jiang Wei,
Zhou Rongbin
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708689
Subject(s) - excellence , china , center of excellence , inflammasome , chinese academy of sciences , medicine , library science , immunology , political science , inflammation , computer science , law
The dysregulation of NLRP 3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP 3 inflammasome are not available in clinic. Here, we show that tranilast ( TR ), an old anti‐allergic clinical drug, is a direct NLRP 3 inhibitor. TR inhibits NLRP 3 inflammasome activation in macrophages, but has no effects on AIM 2 or NLRC 4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP 3 and suppresses the assembly of NLRP 3 inflammasome by blocking NLRP 3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP 3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP 3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP 3‐driven diseases.