The Inhibitory Role of Hydrogen Sulfide in Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

Cystathionine γ-lyase (CSE) is one of the major enzymes producing hydrogen sulfide (H₂S) in lungs, participating in the regulation of respiratory functions. The role of CSE-derived H₂S in eosinophil-dominant inflammation in allergic diseases has been unclear. The objective of this study was to explore the protective role of H₂S against allergen-induced airway hyperresponsiveness (AHR) and inflammation. CSE expression and H₂S production rate were assessed in mouse lung tissues with ovalbumin (OVA)-induced acute asthma. AHR, airway inflammation, and Th2 response in wild-type (WT) mice were compared with those in CSE gene knockout (KO) mice. The effect of NaHS, an exogenous H₂S donor, was also evaluated on these parameters. CSE expression was absent and H₂S production rate was significantly lower in the lungs of CSE KO mice when compared with WT littermates. OVA challenge decreased lung CSE expression and H₂S production in WT mice. CSE deficiency resulted in aggravated AHR, increased airway inflammation, and elevated levels of Th2 cytokines such as IL-5, IL-13, and eotaxin-1 in bronchoalveolar lavage fluid after OVA challenge. The aforementioned alterations were reversed by exogenous H₂S treatment. More importantly, NaHS supplement rescued CSE KO mice from the aggravated pathological process of asthma. The CSE/H₂S system plays a critical protective role in the development of asthma. A new therapeutic potential for asthma via targeting CSE/H₂S metabolism is indicated.