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Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells.

Abstract：

:Hydrogen sulfide (H(2)S) is synthesized intracellularly by the enzymes cystathionine-γ-lyase and cystathionine-β-synthase (CBS), and is proposed to be a gasotransmitter with effects in modulating inflammation and cellular proliferation. We determined a role of H(2)S in airway smooth muscle (ASM) function. ASM were removed from resection or transplant donor lungs and were placed in culture. Proliferation of ASM was induced by FCS and the proinflammatory cytokine, IL-1β. Proliferation of ASM and IL-8 release were measured by bromodeoxyuridine incorporation and ELISA, respectively. Exposure of ASM to H(2)S "donors" inhibited this proliferation and IL-8 release. Methemoglobin, a scavenger of endogenous H(2)S, increased DNA synthesis induced by FCS and IL-1β. In addition, methemoglobin increased IL-8 release induced by FCS, but not by IL-1β, indicating a role for endogenous H(2)S in these systems. Inhibition of CBS, but not cystathionine-γ-lyase, reversed the inhibitory effect of H(2)S on proliferation and IL-8 release, indicating that this is dependent on CBS. CBS mRNA and protein expression were inhibited by H(2)S donors, and were increased by methemoglobin, indicating that CBS is the main enzyme responsible for endogenous H(2)S production. Finally, we found that exogenous H(2)S inhibited the phosphorylation of extracellular signal-regulated kinase-1/2 and p38, which could represent a mechanism by which H(2)S inhibited cellular proliferation and IL-8 release. In summary, H(2)S production provides a novel mechanism for regulation of ASM proliferation and IL-8 release. Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Perry MM,Hui CK,Whiteman M,Wood ME,Adcock I,Kirkham P,Michaeloudes C,Chung KF

doi

10.1165/rcmb.2010-0304OC

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

746-52

issue

eissn

1044-1549

issn

1535-4989

pii

2010-0304OC

journal_volume

pub_type

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Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells.