PMID- 26471297
OWN - NLM
STAT- MEDLINE
DCOM- 20160316
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 467
IP  - 4
DP  - 2015 Nov 27
TI  - Histone deacetylase 6 negatively regulates NLRP3 inflammasome activation.
PG  - 973-8
LID - S0006-291X(15)30734-8 [pii]
LID - 10.1016/j.bbrc.2015.10.033 [doi]
AB  - 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-1beta) 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Hwang, Inhwa
AU  - Hwang I
AD  - Department of Microbiology, Institute for Immunology and Immunological Diseases, 
      Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 120-752, Republic of Korea.
FAU - Lee, Eunju
AU  - Lee E
AD  - Department of Microbiology, Institute for Immunology and Immunological Diseases, 
      Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 120-752, Republic of Korea.
FAU - Jeon, Seon-A
AU  - Jeon SA
AD  - Department of Microbiology, Institute for Immunology and Immunological Diseases, 
      Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 120-752, Republic of Korea.
FAU - Yu, Je-Wook
AU  - Yu JW
AD  - Department of Microbiology, Institute for Immunology and Immunological Diseases, 
      Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul 120-752, Republic of Korea. Electronic address: jewookyu@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151021
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carrier Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Ubiquitin)
RN  - EC 3.5.1.98 (Hdac6 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 6)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Carrier Proteins/*physiology
MH  - Cells, Cultured
MH  - Histone Deacetylase 6
MH  - Histone Deacetylases/*metabolism
MH  - Inflammasomes/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Transcription, Genetic
MH  - Ubiquitin/metabolism
OTO - NOTNLM
OT  - Histone deacetylase 6
OT  - Inflammasome
OT  - NLRP3
EDAT- 2015/10/17 06:00
MHDA- 2016/03/17 06:00
CRDT- 2015/10/17 06:00
PHST- 2015/09/23 00:00 [received]
PHST- 2015/10/07 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2016/03/17 06:00 [medline]
AID - S0006-291X(15)30734-8 [pii]
AID - 10.1016/j.bbrc.2015.10.033 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Nov 27;467(4):973-8. doi: 
      10.1016/j.bbrc.2015.10.033. Epub 2015 Oct 21.