Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/7042148 |
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| author | Yong Li Qi Zhang Na Li Liting Ding Jinping Yi Yue Xiao Shibiao Chen Xuan Huang |
| author_facet | Yong Li Qi Zhang Na Li Liting Ding Jinping Yi Yue Xiao Shibiao Chen Xuan Huang |
| author_sort | Yong Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1ecbbf874d994b12b084de22841b894d |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1ecbbf874d994b12b084de22841b894d2025-02-03T01:00:08ZengWileyMediators of Inflammation1466-18612021-01-01202110.1155/2021/7042148Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1Yong Li0Qi Zhang1Na Li2Liting Ding3Jinping Yi4Yue Xiao5Shibiao Chen6Xuan Huang7Department of AnesthesiologyThe National Engineering Research Center for Bioengineering Drugs and the TechnologiesSchool of Future TechnologyThe National Engineering Research Center for Bioengineering Drugs and the TechnologiesDepartment of Clinical LaboratoryFirst School of Clinical MedicineDepartment of AnesthesiologyThe National Engineering Research Center for Bioengineering Drugs and the TechnologiesEndothelial 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.http://dx.doi.org/10.1155/2021/7042148 |
| spellingShingle | Yong Li Qi Zhang Na Li Liting Ding Jinping Yi Yue Xiao Shibiao Chen Xuan Huang Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 Mediators of Inflammation |
| title | Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 |
| title_full | Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 |
| title_fullStr | Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 |
| title_full_unstemmed | Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 |
| title_short | Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1 |
| title_sort | ataxin 10 inhibits tnf α induced endothelial inflammation via suppressing interferon regulatory factor 1 |
| url | http://dx.doi.org/10.1155/2021/7042148 |
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