Acetylase inhibitor SI-2 is a potent anti-inflammatory agent by inhibiting NLRP3 inflammasome activation |
| |
Affiliation: | 1. Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China;2. Department of Hematology and Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China;3. Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province 410000, PR China |
| |
Abstract: | Aberrant activation of Nod-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in a variety of inflammatory diseases. Targeting NLRP3 inflammasome represents a promising therapy to cure such diseases. We and others recently demonstrated that acetylation of NLRP3 promotes the inflammasome activity and also suggested lysine acetyltransferases inhibitors could be a kind of promising agents for treating NLRP3 associated disorders. In this study, by searching for kinds of lysine acetyltransferases inhibitors, we showed that SI-2 hydrochloride (SI-2), a specific inhibitor of lysine acetyltransferase KAT13B (lysine acetyltransferases 13B), specifically blocks NLRP3 inflammasome activation both in mice in vivo and in human cells ex vivo. Intriguingly, SI-2 does not affect the acetylation of NLRP3. Instead, it disrupts the interaction between NLRP3 and adaptor apoptosis-associated speck-like protein containing CARD (ASC), then blocks the formation of ASC speck. Thus, our study identified a specific inhibitor for NLRP3 inflammasome and suggested SI-2 as a potential inhibitory agent for the therapy of NLRP3-driven diseases. |
| |
Keywords: | SI-2 NLRP3 inflammasome ASC speck |
本文献已被 ScienceDirect 等数据库收录! |
|