Lipopolysaccharide Regulates Cystathionine ? Lyase Expression in Human Umbilical Vein Endothelial Cells via NF ?B Signaling

Abstract

Hydrogen sulfide acts as a signaling molecule that modulates vascular tone, protects against oxidative stress, and functions as an oxygen sensor. Cystathionine ? lyase facilitates the production of hydrogen sulfide, and the cystathionine ? lyase/hydrogen sulfide signaling pathway is implicated in endotoxin induced inflammation, such as that induced by lipopolysaccharide. Therefore, it is essential to examine the expression and regulation of cystathionine ? lyase in human umbilical vein endothelial cells following lipopolysaccharide stimulation. Lipopolysaccharide treatment for 6 h significantly increased cystathionine ? lyase mRNA and protein levels in human umbilical vein endothelial cells. A dual luciferase reporter plasmid pGL4.12 HuCSE710, containing either the wild type of cystathionine ? lyase gene promoter or its mutant variant, was co transfected with the pRL CMV vector into HEK 293T cells. This study investigated the effects of nuclear factor ?B transcription factor binding to this promoter on the transcriptional regulation of the cystathionine ? lyase gene in human umbilical vein endothelial cells after lipopolysaccharide treatment. The DNA sequence GGACATTCC within the cystathionine ? lyase gene promoter was significantly associated with the transcriptional regulation of cystathionine ? lyase in response to lipopolysaccharide treatment. These findings have substantial implications for further research on the regulatory mechanisms of cystathionine ? lyase in inflammation and offer promising insights with potential clinical relevance. Therefore, lipopolysaccharide regulates cystathionine ? lyase expression in human umbilical vein endothelial cells primarily through nuclear factor ?B activation, with the nuclear factor ?B binding site on the cystathionine ? lyase promoter being critical for lipopolysaccharide-induced upregulation and subsequent inflammatory response.