Regulation of Cystathionine γ-Lyase Expression by Lipopolysaccharide in Human Umbilical Vein Endothelial Cells: Involvement of NF-κB Signaling

Abstract

Hydrogen sulfide (H₂S) acts as a signaling molecule that modulates vascular tone, protects against oxidative stress, and functions as an oxygen sensor. Cystathionine γ‑lyase (CSE) facilitates the production of H₂S, and the CSE/H₂S signaling pathway is implicated in endotoxin‑induced inflammation, such as that induced by lipopolysaccharide (LPS). Therefore, it is essential to examine the expression and regulation of CSE in human umbilical vein endothelial cells (HUVECs) following LPS stimulation. LPS treatment for 6 hours significantly increased CSE mRNA and protein levels in HUVECs. A dual‑luciferase reporter plasmid pGL4.12‑HuCSE710, containing either the wild‑type CSE 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‑κB (NF‑κB) transcription factor binding to this promoter on the transcriptional regulation of the CSE gene in HUVECs after LPS treatment. The DNA sequence GGACATTCC within the CSE gene promoter was significantly associated with the transcriptional regulation of CSE in response to LPS treatment. These findings have substantial implications for further research on the regulatory mechanisms of CSE in inflammation and offer promising insights with potential clinical relevance. Therefore, LPS regulates CSE expression in HUVECs primarily through NF‑κB activation, with the NF‑κB binding site on the CSE promoter being critical for LPS‑induced upregulation and subsequent inflammatory response