Effects of hydrogen sulfide on ozone-induced features of chronic obstructive pulmonary disease

Hydrogen sulfide (H 2 S), a novel signaling gasotransmitter in the respiratory system, may have anti-inflammatory properties in the lung. We examined the preventive and therapeutic effects of H 2 S on ozone-induced features of chronic obstructive pulmonary disease (COPD). C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), a donor of H2S, was administered to the mice either before ozone exposure (preventive effect) or after completion of ozone exposure for 6 weeks (therapeutic effect). After 6 weeks of exposure, ozone exposed mice developed emphysema examined by micro-computed tomography (CT) and histology analysis, airflow limitation measured by the forced maneuver system, and increased lung inflammation (increased lung inflammation scores and mRNA levels of IL-1β, IL-18 and MMP-9). Mechanistically, these ozone-induced changes were associated with increased NLRP3-caspase-1 activation and p38 MAPK phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed emphysema and lung inflammation. In contrast, NaHS prevented but did not reverse ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of COPD via regulation of the NLRP3-caspase-1, the p38 MAPK and the Akt pathways.