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 inflammation, and its underlying mechanism. Pro‑inflammatory M1 cytokines (MCP‑1, IL‑1β, and IL‑6) and anti‑inflammatory M2 cytokines (IL‑4 and IL‑10) were detected by RT‑qPCR. CSE, p65 NF‑κB, p‑p65 NF‑κB, IL‑1β, IL‑6 and TNF‑α levels were measured by Western blot. The results revealed that cystathionine γ‑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‑κB phosphorylation and upregulated the expression of inflammatory factors in macrophages. H₂S ameliorated TMAO‑induced activation of the NF‑κB 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 inflammation by reducing P65 NF‑κB phosphorylation via the upregulation and sulfhydration of SIRT1, suggesting that H2S may be used to treat inflammatory vascular diseases.