Metabolic changes of H(2)S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity

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 (H(2)S ) 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. H(2)S 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 H(2)S donor significantly inhibited TNF-α release. Thus, H(2)S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H(2)S protects against CS-induced oxidative stress and inflammation in macrophages and H(2)S on steroid sensitivity deserves further investigation.