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

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.

Exposure to cigarette smoke abrogates the beneficial effect of ischemic postconditioning

“…Both CSE and CBS were found to be reduced following CS exposure. In agreement to this finding, Sun et al (45) reported lower CSE levels in the lungs of smokers. Since H 2 S in known to reduce blood pressure (53), the lower CSE/ CBS expression in CS mice might contribute to the elevated blood pressure seen in this animal cohort.…”

Hydrogen Sulfide Attenuates Particulate Matter-Induced Emphysema and Airway Inflammation Through Nrf2-Dependent Manner

“…Recent study showed that PM was able to induced emphysema and airway inflammation in mice, but the mechanism was not fully understood . In this research, we found that CTH, the main enzyme products H 2 S in lung tissues, was impaired in PMinduced mice emphysema and airway inflammation model, which was consistent with our previous study reported that the protein level of CTH was impaired in smokers and COPD patients (Sun et al, 2015). Moreover, using PPG to inhibit endogenous H 2 S generation aggregated PM-caused lung injury, while the complement of exogenous H 2 S donor NaHS significantly attenuated the PM-induced lung damage.…”

“…We previous reported that hydrogen sulfide (H 2 S), a novel gaseous signal molecule, also severed as defense system in lung, was impaired in COPD patients (Chen et al, 2005;Sun et al, 2015). And H 2 S exerted significant protect role in defending against cigarette smoke or ozone exposure caused COPD/ emphysema via the anti-oxidative stress, anti-apoptosis, antiendoplasmic reticulum stress, anti-inflammatory function of H 2 S (Han et al, 2011;Li F. et al, 2016;Lin et al, 2017).…”

ERS International Congress, Madrid, 2019: highlights from the Basic and Translational Science Assembly

“…Novel H 2 S donors, such as AP39 and RT-O, reduced cigarette smoke-induced ROS levels in vitro in an epithelial ALI culture model and reduced inflammatory cell numbers in the lung and markers of fibrosis in vivo in intranasally smoked mice. Treatment with other antioxidants, such as the mitochondrial-targeted peptide SS-31 and the Nrf2-activating itaconate, showed similar protective effects [71,72,[74][75][76][77]. Thus, mROS scavengers, including mitoQ, SKQ and mitoTempo, may be considered as new potential therapeutics for COPD treatment [70,78].…”

“…H 2 S is an endogenous mitochondrial specific antioxidant, which is both mitochondrial protective and anti-inflammatory [74]. H 2 S has been reported to be reduced in both human COPD and COPD mouse models [75,76], suggesting that the loss of this antioxidant contributes to disease pathology. Novel H 2 S donors, such as AP39 and RT-O, reduced cigarette smoke-induced ROS levels in vitro in an epithelial ALI culture model and reduced inflammatory cell numbers in the lung and markers of fibrosis in vivo in intranasally smoked mice.…”