Li-Ming Yue1, Ya-Mei Gao2, Bao-Hua Han3. 1. Department of Emergency, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, China. 2. Department of Cardiology, Weinan Center Hospital, Weinan, China. 3. Department of Cardiology, The Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, China.
Abstract
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)-1β. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase-1, IL-1β, 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-1β and IL-18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase-1, and IL-1β in THP-1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL-1β 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-1β. 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-1β, 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-1β-nitric oxide (NO) signaling pathway.
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)-1β. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase-1, IL-1β, 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-1β and IL-18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase-1, and IL-1β in THP-1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL-1β 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-1β. 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-1β, 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-1β-nitric oxide (NO) signaling pathway.