0 232

Cited 0 times in

Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4

Authors
 Inhwa Hwang  ;  Jungmin Yang  ;  Sujeong Hong  ;  Eun Ju Lee  ;  Seung-Hyo Lee  ;  Teresa Fernandes-Alnemri  ;  Emad S Alnemri  ;  Je-Wook Yu 
Citation
 Immunology and Cell Biology, Vol.93(6) : 591-599, 2015 
Journal Title
 Immunology and Cell Biology 
ISSN
 0818-9641 
Issue Date
2015
Abstract
Th2 cytokine IL-4 has been previously shown to suppress the production of proinflammatory cytokines in monocytes. However, the underlying molecular mechanism by which IL-4 signaling antagonizes proinflammatory responses is poorly characterized. In particular, whether IL-4 can modulate inflammasome signaling remains unknown. Here, we provide evidence that IL-4 suppresses NLRP3-dependent caspase-1 activation and the subsequent IL-1β secretion but does not inhibit absent in melanoma 2 (AIM2)- or NLRC4 (NOD-like receptor family, CARD domain-containing 4)-dependent caspase-1 activation in THP-1 and mouse bone marrow-derived macrophages. Upon lipopolysaccharide (LPS) or LPS/ATP stimulation, IL-4 markedly inhibited the assembly of NLRP3 inflammasome, including NLRP3-dependent ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) oligomerization, NLRP3-ASC interaction and NLRP3 speck-like oligomeric structure formation. The negative regulation of NLRP3 inflammasome by IL-4 was not due to the impaired mRNA or protein production of NLRP3 and proinflammatory cytokines. Supporting this observation, IL-4 attenuated NLRP3 inflammasome activation even in reconstituted NLRP3-expressing macrophages in which NLRP3 expression is not transcriptionally regulated by TLR-NF-κB signaling. Furthermore, the IL-4-mediated suppression of NLRP3 inflammasome was independent of STAT6-dependent transcription and mitochondrial reactive oxygen species (ROS). Instead, IL-4 inhibited subcellular redistribution of NLRP3 into mitochondria and microtubule polymerization upon NLRP3-activating stimulation. Our results collectively suggest that IL-4 could suppress NLRP3 inflammasome activation in a transcription-independent manner, thus providing an endogenous regulatory machinery to prevent excessive inflammasome activation.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140552
Full Text
http://www.nature.com/icb/journal/v93/n6/full/icb2014125a.html
DOI
10.1038/icb.2014.125
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실)
Yonsei Authors
유제욱(Yu, Je Wook)
Export
RIS (EndNote)
XLS (Excel)
XML
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse