Hydrogen sulfide inhibits NLRP3 inflammasome activation and reduces cytokine production both in vitro and in a mouse model of inflammation.

Details

Serval ID
serval:BIB_61000D21C5FD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Hydrogen sulfide inhibits NLRP3 inflammasome activation and reduces cytokine production both in vitro and in a mouse model of inflammation.
Journal
The Journal of biological chemistry
Author(s)
Castelblanco M., Lugrin J., Ehirchiou D., Nasi S., Ishii I., So A., Martinon F., Busso N.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Publication state
Published
Issued date
16/02/2018
Peer-reviewed
Oui
Volume
293
Number
7
Pages
2546-2557
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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-1β into its active secreted form. Hydrogen sulfide (H <sub>2</sub> S), a gasotransmitter mainly produced by cystathionine γ-lyase (CSE) in macrophages, could modulate inflammation. Here, we sought to investigate the effects of exogenous and endogenous H <sub>2</sub> 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 <sub>2</sub> S donor, sodium thiosulfate (STS) or GYY4137 (GYY). In murine and human macrophages in vitro, both STS and GYY inhibited MSU crystal-induced IL-1β secretion in a dose-dependent manner. Moreover, the H <sub>2</sub> S donors inhibited MSU crystal-induced XO/caspase-1 activities, mitochondrial reactive oxygen species (ROS) generation, and ASC oligomerization. Accordingly, IL-1β 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 <sub>2</sub> S donors) and endogenous (via CSE) H <sub>2</sub> S production may represent approaches for managing, for example, acute gout or other inflammation conditions.
Keywords
Animals, Humans, Hydrogen Sulfide/immunology, Inflammasomes/genetics, Inflammasomes/immunology, Inflammation/genetics, Inflammation/immunology, Interleukin-1beta/genetics, Interleukin-1beta/immunology, Interleukin-6/genetics, Interleukin-6/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein/genetics, NLR Family, Pyrin Domain-Containing 3 Protein/immunology, NLRP3, apoptosis-associated speck-like protein containing a CARD, caspase 1 (CASP1), cystathionine γ-lyase, hydrogen sulfide, inflammasome, monosodium urate, reactive oxygen species (ROS), xanthine oxidase
Pubmed
Web of science
Open Access
Yes
Create date
13/01/2018 11:34
Last modification date
20/08/2019 15:18
Usage data