Back to Search
Start Over
Biphasic inflammatory response induced by intra-plantar injection of L-cysteine: Role of CBS-derived H 2 S and S1P/NO signaling.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Nov; Vol. 167, pp. 115536. Date of Electronic Publication: 2023 Sep 22. - Publication Year :
- 2023
-
Abstract
- This study investigates the inflammatory response to intra-plantar injection of L-cysteine in a murine model. L-cysteine induces a two-phase response: an early phase lasting 6 h and a late phase peaking at 24 h and declining by 192 h. The early phase shows increased neutrophil accumulation at 2 h up to 24 h, followed by a reduction at 48 h. On the other hand, the late phase exhibits increased macrophage infiltration peaking at 96 h. Inhibition of cystathionine β-synthase (CBS), the first enzyme in the transsulfuration pathway, significantly reduces L-cysteine-induced edema, suggesting its dependence on CBS-derived hydrogen sulfide (H <subscript>2</subscript> S). Sequential formation of sphingosine-1-phosphate (S1P) preceding nitric oxide (NO) generation suggests the involvement of a CBS/S1P/NO axis in the inflammatory response. Inhibition of de novo sphingolipid biosynthesis, S1P1 receptor, and endothelial NO synthase (eNOS) attenuates L-cysteine-induced paw edema. These findings indicate a critical role of the CBS/H <subscript>2</subscript> S/S1P/NO signaling pathway in the development and maintenance of L-cysteine-induced inflammation. The co-presence of H <subscript>2</subscript> S and NO is necessary for inducing and sustaining the inflammatory response, as NaHS or L-arginine alone do not replicate the marked and prolonged inflammatory effect observed with L-cysteine. This study enhances our understanding of the complex molecular mechanisms of the interplay between NO and H <subscript>2</subscript> S pathways in inflammation and identifies potential therapeutic targets for inflammatory disorders.<br />Competing Interests: Declaration of Competing Interest None.<br /> (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 167
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 37742608
- Full Text :
- https://doi.org/10.1016/j.biopha.2023.115536