Evaluation on the effect of hydrogen sulfide on the NLRP3 signaling pathway and its involvement in the pathogenesis of atherosclerosis.

BACKGROUND: As a common disease, the incidence of atherosclerosis (AS) in the world is high. Therefore, we aimed to evaluate the involvement of hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) in the pathogenesis of AS as well as their possible signaling pathways. METHODS: Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis were used to detect the effect of CSE on the expression of inflammatory cytokines, ie, H 2 S, thioredoxin-interacting protein (TXNIP), NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, and interleukin (IL)-1ß. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase-1, IL-1ß, and IL-18 among different groups. RESULT: Knockdown of CSE by the transfection of CSE small interfering RNA upregulated the levels of two inflammatory cytokines, ie, IL-1ß and IL-18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase-1, and IL-1ß in THP-1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL-1ß and IL-18. Furthermore, upregulation of H 2 S synthesis by treating the cells with NaHS also reduced the protein levels of TXNIP, NLRP3, ASC, caspase-1, and IL-1ß. Finally, the protein levels of TXNIP and NLRP3 in the AS group were much higher than those in the AS + H 2 S group, which in turn was higher than the sham group. In addition, the AS group displayed the highest protein levels of TXNIP, NLRP3, ASC, caspase-1, IL-1ß, and IL-18, while the levels of these proteins in the AS + H 2 S group were higher than those in the sham group. CONCLUSION: In summary, the present finding suggested a possible linkage between H 2 S metabolism and AS through the H 2 S/CSE-TXNIP-NLRP3-IL-18/IL-1ß-nitric oxide (NO) signaling pathway.