RRC ID 51883
Author Wu WJ, Jia WW, Liu XH, Pan LL, Zhang QY, Yang D, Shen XY, Liu L, Zhu YZ.
Title S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway.
Journal Redox Biol
Abstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), 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 H2S 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 H2S 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 H2S modulator, exerted anti-inflammatory properties in RA by upregulating the Nrf2-antioxidant response element (ARE) signaling pathway.
Volume 10
Pages 157-167
Published 2016-12
DOI 10.1016/j.redox.2016.08.011
PII S2213-2317(16)30122-7
PMID 27744121
PMC PMC5066299
MeSH Animals Anti-Inflammatory Agents / administration & dosage* Anti-Inflammatory Agents / pharmacology Antioxidant Response Elements / drug effects* Arthritis, Rheumatoid / drug therapy* Arthritis, Rheumatoid / genetics Cell Line Cell Movement / drug effects Cell Survival Cysteine / administration & dosage Cysteine / analogs & derivatives* Cysteine / pharmacology Disease Models, Animal Dose-Response Relationship, Drug Humans Male NF-E2-Related Factor 2 / genetics* Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Signal Transduction / drug effects Up-Regulation
IF 7.126
Human and Animal Cells MH7A(RCB1512)