Cutting Edge: G Protein Subunit β 1 Negatively Regulates NLRP3 Inflammasome Activation

被引：19

作者：

Murakami, Tomohiko ^{[1
]}

Ruengsinpinya, Lerdluck ^{[1
]}

Nakamura, Eriko ^{[1
]}

Takahata, Yoshifumi ^{[1
]}

Hata, Kenji ^{[1
]}

Okae, Hiroaki ^{[2
,3
]}

Taniguchi, Shun'ichiro ^{[4
]}

Takahashi, Masafumi ^{[5
]}

Nishimura, Riko ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Dent, Dept Mol & Cellular Biochem, 1-8 Yamada Oka, Suita, Osaka 5650871, Japan

[2] Tohoku Univ, Grad Sch Med, Dept Informat Genet Environm, Sendai, Miyagi 9808575, Japan

[3] Tohoku Univ, Grad Sch Med, Genome Res Ctr, Sendai, Miyagi 9808575, Japan

[4] Shinshu Univ, Sch Med, Dept Comprehens Canc Therapy, Nagano 3908621, Japan

[5] Jichi Med Univ, Ctr Mol Med, Div Inflammat Res, Shimotsuke, Tochigi 3290498, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2019年 / 202卷 / 07期

基金：

日本学术振兴会;

关键词：

INHIBITION; CA2+; ASC;

D O I：

10.4049/jimmunol.1801388

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The NLRP3 inflammasome has important roles in the pathogenesis of various inflammatory diseases. However, the regulatory mechanisms of the NLRP3 inflammasome are not fully understood. In this study, we attempted to identify molecules that interact with NLRP3 upon its activation. We identified G protein subunit beta 1 (GNB1), a downstream molecule of G protein coupled receptors (GPCRs), which regulates the NLRP3 inflammasome activation. GNB1 was physically associated with NLRP3 via the pyrin domain of NLRP3. Activation of the NLRP3 inflammasome was enhanced in GNB1-knockdown or GNB1-deficient murine macrophages, although a lack of GNB1 did not affect activation of the AIM2 inflammasome. ASC oligomerization induced by NLRP3 was enhanced by GNB1 deficiency. Conversely, NLRP3-dependent ASC oligomerization was inhibited by the overexpression of GNB1. This study indicates that GNB1 negatively regulates NLRP3 inflammasome activation by suppressing NLRP3-dependent ASC oligomerization, and it provides a regulatory mechanism of the NLRP3 inflammasome.

引用

页码：1942 / 1947

页数：6

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