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Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1.
Li, Yong; Zhang, Qi; Li, Na; Ding, Liting; Yi, Jinping; Xiao, Yue; Chen, Shibiao; Huang, Xuan.
Affiliation
  • Li Y; Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • Zhang Q; The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
  • Li N; School of Future Technology, Nanchang University, Nanchang, China.
  • Ding L; The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
  • Yi J; Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • Xiao Y; First School of Clinical Medicine, Nanchang University, Nanchang, China.
  • Chen S; Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • Huang X; The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
Mediators Inflamm ; 2021: 7042148, 2021.
Article in En | MEDLINE | ID: mdl-34858081
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-κB 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Necrosis Factor-alpha / Endothelial Cells / Interferon Regulatory Factor-1 / Ataxin-10 / Inflammation Type of study: Etiology_studies / Prognostic_studies Limits: Humans Language: En Journal: Mediators Inflamm Journal subject: BIOQUIMICA / PATOLOGIA Year: 2021 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Necrosis Factor-alpha / Endothelial Cells / Interferon Regulatory Factor-1 / Ataxin-10 / Inflammation Type of study: Etiology_studies / Prognostic_studies Limits: Humans Language: En Journal: Mediators Inflamm Journal subject: BIOQUIMICA / PATOLOGIA Year: 2021 Type: Article Affiliation country: China