Hydrogen sulfide suppresses ox-LDL-stimulated monocyte chemoattractant protein-1 generation from macrophages via NF-{kappa}B pathway [Cell Biology]

February 18th, 2014 by Du, J., Huang, Y., Yan, H., Zhang, Q., Zhao, M., Zhu, M., Liu, J., Chen, S. X., Bu, D., Tang, C., Jin, H.

Abstract The study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein-1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS), hexyl acrylate (HA) and then treated with ox-LDL. The results showed that ox-LDL treatment downregulated the H2S/cystathionie-β-synthase (CBS) pathway, with increased MCP-1 protein and mRNA expressions in both THP-1 cells and RAW macrophages. HA promoted ox-LDL-induced inflammation, while the H2S donor NaHS inhibited it. NaHS markedly suppressed nuclear factor-κB (NF-κB) p65 phosphorylation, nuclear translocation, DNA binding activity and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-[kappa]B and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity and recruitment to the MCP-1 promoter.The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in oxLDL-induced macrophage inflammation.
  • Posted in Journal of Biological Chemistry, Publications
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