Exogenous hydrogen sulfide inhibits oral mucosal wound-induced macrophage activation via the NF-κB pathway

Objective: This study includes exploring (i) the production of endogenous hydrogen sulfide (H₂S) after mucosal wound generation and (ii) the role of compensating the change in H₂S level postmucosal wound generation. Methods and Materials: A mucosal wound model was established in female C57BL/6J mice. Wound tissues were collected to examine the change in the endogenous H₂S level. To examine the effect of decreased H₂S, GYY4137 was intraperitoneally injected into mice at 50 mg kg⁻¹ day⁻¹ before mucosal wounding to compensate for the decreased endogenous H₂S. Finally, we confirmed the role of GYY4137 in inhibiting the M1 phenotype macrophage activation induced by LPS in peritoneal macrophages and RAW264.7. Results: The production of endogenous H₂S and the expression of cystathionine b-synthase and cystathionine g-lyase in vivo were reduced significantly in early stage after wound. GYY4137 significantly inhibited the activation of the M1 phenotype induced by mucosal wound inflammation in vivo and LPS in vitro. Finally, we confirmed that GYY4137 inhibited iNOS expression via the NF-κB signaling pathway. Conclusion: The exogenous H₂S donor GYY4137 compensated for the reduced endogenous H₂S postmucosal wound generation and inhibited the induced M1 macrophage activation. Thus, appropriate H₂S supplementation may aid in controlling inflammation associated with mucosal wounds.