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

This study includes exploring (i) the production of endogenous hydrogen sulfide (H₂ S) after mucosal wound generation and (ii) the role of compensating the change in H₂ S level postmucosal wound generation.

A mucosal wound model was established in female C57BL/6J mice. Wound tissues were collected to examine the change in the endogenous H₂ S level. To examine the effect of decreased H₂ S, GYY4137 was intraperitoneally injected into mice at 50 mg kg^-1  day^-1 before mucosal wounding to compensate for the decreased endogenous H₂ S. Finally, we confirmed the role of GYY4137 in inhibiting the M1 phenotype macrophage activation induced by LPS in peritoneal macrophages and RAW264.7.

The production of endogenous H₂ S 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.

The exogenous H₂ S donor GYY4137 compensated for the reduced endogenous H₂ S postmucosal wound generation and inhibited the induced M1 macrophage activation. Thus, appropriate H₂ S supplementation may aid in controlling inflammation associated with mucosal wounds.