PMID- 29279328
OWN - NLM
STAT- MEDLINE
DCOM- 20190205
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 293
IP  - 7
DP  - 2018 Feb 16
TI  - Hydrogen sulfide inhibits NLRP3 inflammasome activation and reduces cytokine 
      production both in vitro and in a mouse model of inflammation.
PG  - 2546-2557
LID - 10.1074/jbc.M117.806869 [doi]
AB  - A variety of stimuli, including monosodium urate (MSU) crystals, activate the 
      NLRP3 inflammasome, and this activation involves several molecular mechanisms 
      including xanthine oxidase (XO) up-regulation and mitochondrial dysfunction. Upon 
      oligomerization of apoptosis-associated speck-like protein containing a CARD 
      (ASC), caspase-1 becomes active and cleaves the proinflammatory cytokine IL-1beta 
      into its active secreted form. Hydrogen sulfide (H(2)S), a gasotransmitter mainly 
      produced by cystathionine gamma-lyase (CSE) in macrophages, could modulate 
      inflammation. Here, we sought to investigate the effects of exogenous and 
      endogenous H(2)S on NLRP3 inflammasome activation in vitro and in vivo Primed 
      bone marrow-derived macrophages (BMDM) isolated from wildtype (wt) or 
      CSE-deficient mice and human macrophages (THP1 cells and primary macrophages), 
      were stimulated with MSU crystals in the presence or absence of a H(2)S donor, 
      sodium thiosulfate (STS) or GYY4137 (GYY). In murine and human macrophages in 
      vitro, both STS and GYY inhibited MSU crystal-induced IL-1beta secretion in a 
      dose-dependent manner. Moreover, the H(2)S donors inhibited MSU crystal-induced 
      XO/caspase-1 activities, mitochondrial reactive oxygen species (ROS) generation, 
      and ASC oligomerization. Accordingly, IL-1beta secretion and XO/caspase-1 activities 
      were higher in CSE-deficient BMDMs than in wt BMDMs. For in vivo studies, we 
      experimentally induced peritonitis by intraperitoneal injection of MSU crystals 
      into mice. GYY pretreatment ameliorated inflammation, evidenced by decreased 
      IL-6/monocyte chemoattractant protein-1 (MCP-1) released into peritoneal lavages. 
      Taken together, our results suggest that both exogenous (via H(2)S donors) and 
      endogenous (via CSE) H(2)S production may represent approaches for managing, for 
      example, acute gout or other inflammation conditions.
CI  - (c) 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Castelblanco, Mariela
AU  - Castelblanco M
AD  - From the Service of Rheumatology, DAL, Lausanne University Hospital (CHUV) and.
FAU - Lugrin, Jerome
AU  - Lugrin J
AD  - the Department of Biochemistry, University of Lausanne, Epalinges 155 1066, 
      Switzerland and.
FAU - Ehirchiou, Driss
AU  - Ehirchiou D
AD  - the Department of Biochemistry, University of Lausanne, Epalinges 155 1066, 
      Switzerland and.
FAU - Nasi, Sonia
AU  - Nasi S
AD  - From the Service of Rheumatology, DAL, Lausanne University Hospital (CHUV) and.
FAU - Ishii, Isao
AU  - Ishii I
AD  - Showa Pharmaceutical University, Tokyo 194-8543, Japan.
FAU - So, Alexander
AU  - So A
AD  - From the Service of Rheumatology, DAL, Lausanne University Hospital (CHUV) and.
FAU - Martinon, Fabio
AU  - Martinon F
AD  - the Department of Biochemistry, University of Lausanne, Epalinges 155 1066, 
      Switzerland and.
FAU - Busso, Nathalie
AU  - Busso N
AD  - From the Service of Rheumatology, DAL, Lausanne University Hospital (CHUV) and 
      Nathalie.Busso@chuv.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171226
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Nlrp3 protein, mouse)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Hydrogen Sulfide/*immunology
MH  - Inflammasomes/genetics/*immunology
MH  - Inflammation/genetics/*immunology
MH  - Interleukin-1beta/genetics/immunology
MH  - Interleukin-6/genetics/immunology
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*immunology
PMC - PMC5818172
OTO - NOTNLM
OT  - NLRP3
OT  - apoptosis-associated speck-like protein containing a CARD
OT  - caspase 1 (CASP1)
OT  - cystathionine gamma-lyase
OT  - hydrogen sulfide
OT  - inflammasome
OT  - monosodium urate
OT  - reactive oxygen species (ROS)
OT  - xanthine oxidase
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2017/12/28 06:00
MHDA- 2019/02/06 06:00
PMCR- 2019/02/16
CRDT- 2017/12/28 06:00
PHST- 2017/07/21 00:00 [received]
PHST- 2017/11/17 00:00 [revised]
PHST- 2017/12/28 06:00 [pubmed]
PHST- 2019/02/06 06:00 [medline]
PHST- 2017/12/28 06:00 [entrez]
PHST- 2019/02/16 00:00 [pmc-release]
AID - S0021-9258(20)31715-4 [pii]
AID - M117.806869 [pii]
AID - 10.1074/jbc.M117.806869 [doi]
PST - ppublish
SO  - J Biol Chem. 2018 Feb 16;293(7):2546-2557. doi: 10.1074/jbc.M117.806869. Epub 
      2017 Dec 26.