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Evaluation on the effect of hydrogen sulfide on the NLRP3 signaling pathway and its involvement in the pathogenesis of atherosclerosis
Author(s) -
Yue LiMing,
Gao YaMei,
Han BaoHua
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27404
Subject(s) - txnip , sodium hydrosulfide , thioredoxin interacting protein , downregulation and upregulation , western blot , pathogenesis , chemistry , gene knockdown , caspase 1 , signal transduction , small interfering rna , inflammasome , microbiology and biotechnology , interleukin 18 , apoptosis , transfection , medicine , thioredoxin , biology , immunology , biochemistry , hydrogen sulfide , cytokine , enzyme , receptor , sulfur , organic chemistry , gene
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.