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Histone deacetylase 6 negatively regulates NLRP3 inflammasome activation

Authors
 Inhwa Hwang  ;  Eunju Lee  ;  Seon-A Jeon  ;  Je-Wook Yu 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.467(4) : 973-978, 2015 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2015
MeSH
Animals ; Binding Sites ; Carrier Proteins/physiology* ; Cells, Cultured ; Histone Deacetylase 6 ; Histone Deacetylases/metabolism* ; Inflammasomes/physiology* ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; Transcription, Genetic ; Ubiquitin/metabolism
Keywords
Histone deacetylase 6 ; Inflammasome ; NLRP3
Abstract
Emerging reports demonstrate that deregulated NLRP3 inflammasome activation is implicated in a variety of inflammatory and metabolic disorders, but the molecular mechanism underlying NLRP3 inflammasome regulation remains uncertain. Here, we present evidence that histone deacetylase 6 (HDAC6) inhibits the activation of NLRP3 inflammasome through its direct association with NLRP3. ShRNA-mediated knockdown of HDAC6 in bone marrow-derived macrophages (BMDMs) showed a significant increase in caspase-1 activation and interleukin-1 beta (IL-1β) secretion in response to NLRP3-activating stimulations, but not to absent in melanoma 2 (AIM2)-activating stimulation. In addition, knockdown of HDAC6 in BMDMs enhanced the oligomerization of ASC upon LPS/nigericin stimulation. The augmented NLRP3 inflammasome activation seen in HDAC6-knockdown BMDMs is independent of the deacetylase activity of HDAC6. Instead, HDAC6 directly associates with NLRP3 through its ubiquitin-binding domain. Moreover, PR619 treatment (deubiquitinase inhibitor) resulted in the elevation in the interaction of NLRP3 with HDAC6 and the decrease in NLRP3-dependent caspase-1 activation. Taken together, our results indicate that HDAC6 negatively regulates NLRP3 inflammasome activation through its interaction to ubiquitinated NLRP3.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X15307348
DOI
10.1016/j.bbrc.2015.10.033
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
Hwang, Inhwa(황인화) ORCID logo https://orcid.org/0000-0001-5235-3519
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156737
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