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S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway.
- Source :
-
Redox biology [Redox Biol] 2016 Dec; Vol. 10, pp. 157-167. Date of Electronic Publication: 2016 Oct 06. - Publication Year :
- 2016
-
Abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H <subscript>2</subscript> S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H <subscript>2</subscript> S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1β-induced human rheumatoid fibroblast-like synoviocytes MH7A. In addition, SPRC blocked IL-1β-mediated migration and invasion of MH7A cells. As expected, the protective effects of SPRC were partially abrogated by DL-propargylglycine (PAG, a H <subscript>2</subscript> S biosynthesis inhibitor). In vivo study also demonstrated that SPRC treatment markedly ameliorated the severity of RA in adjuvant-induced arthritis rats, and this effect was associated with the inhibition of inflammatory response. We further identified that SPRC remarkably induced heme oxygenase-1 expression associated with the degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); this effect was attributed to the sulfhydrylation of the cysteine residue of Keap1. Our data demonstrated for the first time that SPRC, an endogenous H <subscript>2</subscript> S modulator, exerted anti-inflammatory properties in RA by upregulating the Nrf2-antioxidant response element (ARE) signaling pathway.<br /> (Copyright © 2016. Published by Elsevier B.V.)
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Arthritis, Rheumatoid genetics
Cell Line
Cell Movement drug effects
Cell Survival
Cysteine administration & dosage
Cysteine pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Humans
Male
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Up-Regulation
Anti-Inflammatory Agents administration & dosage
Antioxidant Response Elements drug effects
Arthritis, Rheumatoid drug therapy
Cysteine analogs & derivatives
NF-E2-Related Factor 2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2213-2317
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Redox biology
- Publication Type :
- Academic Journal
- Accession number :
- 27744121
- Full Text :
- https://doi.org/10.1016/j.redox.2016.08.011