The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide.

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Title: The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide.
Authors: Perry, MM
Tildy, B
Papi, A
Casolari, P
Caramori, G
Rempel, KL
Halayko, AJ
Adcock, I
Chung, KF
Item Type: Journal Article
Abstract: BACKBROUND: COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H2S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. METHODS: We examined the effect of H2S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. RESULTS: Exposure of ASM to H2S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H2S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H2S donors. Finally, we report that exogenous H2S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. CONCLUSIONS: H2S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H2S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H2S production.
Issue Date: 9-May-2018
Date of Acceptance: 23-Apr-2018
ISSN: 1465-9921
Publisher: BioMed Central
Journal / Book Title: Respiratory Research
Volume: 19
Issue: 1
Copyright Statement: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Commission of the European Communities
Asthma UK
Funder's Grant Number: 115010
Keywords: Airway smooth muscle
Hydrogen sulfide
1102 Cardiovascular Medicine And Haematology
1103 Clinical Sciences
Respiratory System
Publication Status: Published
Conference Place: England
Article Number: ARTN 85
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine

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