Hydrogen sulfide attenuates TMAO-induced macrophage inflammation through increased SIRT1 sulfhydration

Chronic inflammation is a key factor that accelerates the progression of inflammatory vascular disease. Hydrogen sulfide (H2S) has potent anti-inflammatory effects; however, its underlying mechanism of action has not been fully elucidated. The present study aimed to investigate the potential effect of H2S on sirtuin 1 (SIRT1) sulfhydration in trimethylamine N-oxide (TMAO) -induced macrophage in.ammation, and its underlying mechanism. Pro-inflammatory M1 cytokines (MCP-1, IL-1 beta, and IL-6) and anti-inflammatory M2 cytokines (IL-4 and IL-10) were detected by RT-qPCR. CSE, p65 NF-kappa B, p-p65 NF-kappa B, IL-1 beta, IL-6 and TNF-alpha levels were measured by Western blot. The results revealed that cystathionine gamma-lyase protein expression was negatively associated with TMAO-induced inflammation. Sodium hydrosulfide (a donor of H2S) increased SIRT1 expression and inhibited the expression of inflammatory cytokines in TMAO-stimulated macrophages. Furthermore, nicotinamide, a SIRT1 inhibitor, antagonized the protective effect of H2S, which contributed to P65 NF-kappa B phosphorylation and upregulated the expression of inflammatory factors in macrophages. H2S ameliorated TMAO-induced activation of the NF-kappa B signaling pathway via SIRT1 sulfhydration. Moreover, the antagonistic effect of H2S on inflammatory activation was largely eliminated by the desulfhydration reagent dithiothreitol. These results indicated that H2S may prevent TMAO-induced macrophage in.ammation by reducing P65 NF-kappa B phosphorylation via the upregulation and sulfhydration of SIRT1, suggesting that H2S may be used to treat in.ammatory vascular diseases.