Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity

Yun Sun; Keyi Wang; Min-Xia Li; Wei He; Jin-Rui Chang; Cheng-Cheng Liao; Fan Lin; Yong-Fen Qi; Rui Wang; Ya-Hong Chen

doi:10.1038/srep14971

Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity

Sci Rep. 2015 Oct 12:5:14971. doi: 10.1038/srep14971.

Authors

Yun Sun¹, Keyi Wang², Min-Xia Li¹, Wei He², Jin-Rui Chang³, Cheng-Cheng Liao¹, Fan Lin¹, Yong-Fen Qi³, Rui Wang⁴, Ya-Hong Chen¹

Affiliations

¹ Pulmonary and Critical Care Medicine Department, Peking University Third Hospital, Beijing 100191, China.
² Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191, China.
³ Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
⁴ Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada.

Abstract

Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Hormones / pharmacology*
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line, Tumor
Cystathionine beta-Synthase / genetics
Cystathionine beta-Synthase / metabolism
Cystathionine gamma-Lyase / genetics
Cystathionine gamma-Lyase / metabolism
Dexamethasone / pharmacology
Gene Expression Regulation
Glutathione / metabolism
Humans
Hydrogen Sulfide / metabolism
Hydrogen Sulfide / pharmacology
Inflammation / etiology
Inflammation / metabolism
Inflammation / pathology
Interleukin-8 / genetics
Interleukin-8 / metabolism
Lipopolysaccharides / pharmacology
Lung / drug effects
Lung / metabolism*
Lung / pathology
Macrophages / drug effects
Macrophages / metabolism*
Macrophages / pathology
Oxidative Stress
Pulmonary Disease, Chronic Obstructive / drug therapy
Pulmonary Disease, Chronic Obstructive / genetics
Pulmonary Disease, Chronic Obstructive / metabolism*
Pulmonary Disease, Chronic Obstructive / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism*
Rats
Rats, Sprague-Dawley
Signal Transduction
Smoking / adverse effects
Sulfides / metabolism
Sulfides / pharmacology
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism

Substances

Adrenal Cortex Hormones
Anti-Inflammatory Agents
Interleukin-8
Lipopolysaccharides
RNA, Messenger
Sulfides
Tumor Necrosis Factor-alpha
Dexamethasone
Superoxide Dismutase
Cystathionine beta-Synthase
Cystathionine gamma-Lyase
sodium bisulfide
Glutathione
Hydrogen Sulfide