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Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage.
Cell Signal. 2013 Nov; 25(11):2255-62.CS

Abstract

Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. The present study showed that the levels of CSE mRNA and protein expression, as well as H2S production were decreased in ox-LDL-treated macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis factor-α (TNF-α) generation in Raw264.7 and primary macrophage while CSE knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also decreased the production of TNF-α and intercellular adhesion molecule-1 (ICAM-1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to endothelial monolayer. Cysteine, a CSE preferential substrate for H2S biosynthesis, produced similar effects on the pro-inflammatory cytokine generation, which were reversed by CSE inhibitors PAG and BCA, respectively. Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of IκBα and p65 nuclear translocation, as well as JNK activation caused by ox-LDL. The JNK inhibitor suppressed the NF-κB transcription activity in ox-LDL-treated cells. Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway.

Authors+Show Affiliations

Institute of Neuroscience, Soochow University, Suzhou 215123, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23872072

Citation

Wang, Xian-Hui, et al. "Dysregulation of Cystathionine Γ-lyase (CSE)/hydrogen Sulfide Pathway Contributes to ox-LDL-induced Inflammation in Macrophage." Cellular Signalling, vol. 25, no. 11, 2013, pp. 2255-62.
Wang XH, Wang F, You SJ, et al. Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage. Cell Signal. 2013;25(11):2255-62.
Wang, X. H., Wang, F., You, S. J., Cao, Y. J., Cao, L. D., Han, Q., Liu, C. F., & Hu, L. F. (2013). Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage. Cellular Signalling, 25(11), 2255-62. https://doi.org/10.1016/j.cellsig.2013.07.010
Wang XH, et al. Dysregulation of Cystathionine Γ-lyase (CSE)/hydrogen Sulfide Pathway Contributes to ox-LDL-induced Inflammation in Macrophage. Cell Signal. 2013;25(11):2255-62. PubMed PMID: 23872072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage. AU - Wang,Xian-Hui, AU - Wang,Fen, AU - You,Shou-Jiang, AU - Cao,Yong-Jun, AU - Cao,Li-Dan, AU - Han,Qiao, AU - Liu,Chun-Feng, AU - Hu,Li-Fang, Y1 - 2013/07/18/ PY - 2013/06/22/received PY - 2013/07/11/accepted PY - 2013/7/23/entrez PY - 2013/7/23/pubmed PY - 2014/3/19/medline KW - ApoE KW - BCA KW - CBS KW - CSE KW - Cystathionine-γ-lyase KW - H(2)S KW - HUVEC KW - Hydrogen sulfide KW - ICAM-1 KW - Inflammation KW - JNK KW - LDL KW - Macrophage KW - Oxidized-LDL KW - PAG KW - SMC KW - TNF-α KW - apolipoprotein E KW - cystathionine γ-lyase KW - cystathionine-β-synthase KW - dl-propargylglycine KW - human umbilical vein endothelial cells KW - hydrogen sulfide KW - intercellular adhesion molecule-1 KW - low-density lipoprotein KW - ox-LDL KW - oxidized LDL KW - smooth muscle cell KW - tumor necrosis factor-α KW - β-cyano-l-alanine SP - 2255 EP - 62 JF - Cellular signalling JO - Cell Signal VL - 25 IS - 11 N2 - Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. The present study showed that the levels of CSE mRNA and protein expression, as well as H2S production were decreased in ox-LDL-treated macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis factor-α (TNF-α) generation in Raw264.7 and primary macrophage while CSE knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also decreased the production of TNF-α and intercellular adhesion molecule-1 (ICAM-1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to endothelial monolayer. Cysteine, a CSE preferential substrate for H2S biosynthesis, produced similar effects on the pro-inflammatory cytokine generation, which were reversed by CSE inhibitors PAG and BCA, respectively. Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of IκBα and p65 nuclear translocation, as well as JNK activation caused by ox-LDL. The JNK inhibitor suppressed the NF-κB transcription activity in ox-LDL-treated cells. Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/23872072/Dysregulation_of_cystathionine_γ_lyase__CSE_/hydrogen_sulfide_pathway_contributes_to_ox_LDL_induced_inflammation_in_macrophage_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(13)00208-8 DB - PRIME DP - Unbound Medicine ER -