hydrogen sulfide attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in vascular endothelial cells硫化氢减毒肿瘤坏死factor-α-induced炎症信号,在血管内皮细胞功能障碍.pdfVIP

Hydrogen Sulfide Attenuated Tumor Necrosis Factor-a- Induced Inflammatory Signaling and Dysfunction in Vascular Endothelial Cells 1. 1. 1 1 1,2 Li-Long Pan , Xin-Hua Liu , Qi-Hai Gong , Dan Wu , Yi-Zhun Zhu * 1 Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China, 2 Institute of Biomedical Sciences, Fudan University, Shanghai, China Abstract Background: Hydrogen sulfide (H S), the third physiologically relevant gaseous molecule, is recognized increasingly as an 2 anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H2S donor) on tumor necrosis factor (TNF)-a-induced human umbilical vein endothelial cells (HUVEC) dysfunction. Methodology and Principal Findings: Application of NaHS concentration-dependently suppressed TNF-a-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti- inflammatory action of NaHS. Furthermore, TNF-a-induced NF-kB activation assessed by IkBa degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS. Significance: H S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up- 2 regulation of HO-1. Citation: Pan L-L, Liu X-H