Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1. (23rd November 2021)

• Record Type: Journal Article
• Authors: Li, Yong; Zhang, Qi; Li, Na; Ding, Liting; Yi, Jinping; Xiao, Yue; Chen, Shibiao; Huang, Xuan
• Other Names: UGUSMAN AZIZAH Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2021(2021)
• Publication Date: 2021-11-23
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2021/7042148
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Endothelial inflammation is a crucial event in the initiation of atherosclerosis. Here, we identify Ataxin-10 protein as a novel negative modulator of endothelial activation by suppressing IRF-1 transcription activity. The protein level of Ataxin-10 is relatively higher in human vascular endothelial cells, which can be significantly suppressed by TNF- α in both HUVECs and HLMECs. Overexpression of Ataxin-10 markedly inhibited the mRNA expressions of VCAM-1 and several cytokines including MCP-1, CXCL-1, CCL-5, and TNF- α ; thus, it can also suppress monocyte adhesion to endothelial cells. Accordingly, Ataxin-10 silencing promoted endothelial inflammation. However, Ataxin-10 did not affect the MAPK/NF- κ B signaling pathway stimulated by TNF- α in HUVECs. Using the yeast two-hybrid assay, we found that Ataxin-10 can directly bind to interferon regulatory factor-1 (IRF-1). Upon TNF- α stimulation, Ataxin-10 promoted the cytoplasmic localization of IRF-1, which inhibited the transcription of VCAM-1. Moreover, knockdown of IRF-1 can eliminate the effect of Ataxin-10 on the expression of VCAM-1 in HUVECs induced by TNF- α . Taken together, these results indicate that Ataxin-10 inhibits endothelial cell activation and may serve as a promising therapeutic target for some vascular inflammatory-related diseases such as atherosclerosis.