Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1.
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.
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