Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B
Background. This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods. The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus oc...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/6909764 |
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| author | Yunyan Li Jianfu Chen Yuan Yang Yuxue Wang Yong Zhang Yan Zhou Yan Bao Zongmei Zhang Yongping Lu |
| author_facet | Yunyan Li Jianfu Chen Yuan Yang Yuxue Wang Yong Zhang Yan Zhou Yan Bao Zongmei Zhang Yongping Lu |
| author_sort | Yunyan Li |
| collection | DOAJ |
| description | Background. This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods. The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus occupied the entire venous lumen at 48 h after ligation. Meanwhile, the increased expression of p-RIP3/RIP3 was most pronounced at 48 h after ligation, and the p-MLKL/MLKL peaked at 72 h. Results. Based on Illumina sequencing and KEGG pathway analyses, the activated RIP3/MLKL is associated with increased IL-17B. With thrombus formation, IL-17B was upregulated and enhanced the expression of RIP3 and MLKL in the IVC wall, as well as their phosphorylation levels (all P<0.05, the comparison group consisted of the control group, DVT group, DVT/IL-17B group, and DVT/anti-IL-17B group). The p-RIP3/RIP3 and p-MLKL/MLKL ratios were reduced by anti-IL-17B. Similarly, the weight and cross-sectional area of the thrombi were increased by IL-17B and decreased by the IL-17B antibody. IL-17B had a smaller effect on thrombosis in knockout mice compared with WT mice. In vitro, the IL-17B protein expression and the level of RIP3 and MLKL phosphorylation increased high in the OGD cells, accompanied by increased expression of IL-6 and TNF-α. IL-17B enhanced the expression of IL-6 and TNF-α but had little effect on the IL-6 and TNF-α after transfected with siRIP3 or siMLKL. Similarly, the plasma IL-17B, IL-6, and TNF-α were significantly increased after thrombosis in WT mice, and enhanced by IL-17B. But IL-17B did not increase the plasma IL-6 and TNF-α in knockout mice. Conclusions. In conclusion, those results suggest that vascular endothelial necroptosis plays a crucial role in vascular injury and IL-17B could enhance the necroptosis pathway. |
| format | Article |
| id | doaj-art-90b2ae25079c40d4ab118fe8be63e56e |
| institution | DOAJ |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-90b2ae25079c40d4ab118fe8be63e56e2025-08-20T03:20:32ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/6909764Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17BYunyan Li0Jianfu Chen1Yuan Yang2Yuxue Wang3Yong Zhang4Yan Zhou5Yan Bao6Zongmei Zhang7Yongping Lu8Department of UltrasoundDepartment of UltrasoundDepartment of UltrasoundDepartment of UltrasoundDepartment of UltrasoundDepartment of UltrasoundDepartment of Vascular SurgeryDepartment of PathologyDepartment of UltrasoundBackground. This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods. The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus occupied the entire venous lumen at 48 h after ligation. Meanwhile, the increased expression of p-RIP3/RIP3 was most pronounced at 48 h after ligation, and the p-MLKL/MLKL peaked at 72 h. Results. Based on Illumina sequencing and KEGG pathway analyses, the activated RIP3/MLKL is associated with increased IL-17B. With thrombus formation, IL-17B was upregulated and enhanced the expression of RIP3 and MLKL in the IVC wall, as well as their phosphorylation levels (all P<0.05, the comparison group consisted of the control group, DVT group, DVT/IL-17B group, and DVT/anti-IL-17B group). The p-RIP3/RIP3 and p-MLKL/MLKL ratios were reduced by anti-IL-17B. Similarly, the weight and cross-sectional area of the thrombi were increased by IL-17B and decreased by the IL-17B antibody. IL-17B had a smaller effect on thrombosis in knockout mice compared with WT mice. In vitro, the IL-17B protein expression and the level of RIP3 and MLKL phosphorylation increased high in the OGD cells, accompanied by increased expression of IL-6 and TNF-α. IL-17B enhanced the expression of IL-6 and TNF-α but had little effect on the IL-6 and TNF-α after transfected with siRIP3 or siMLKL. Similarly, the plasma IL-17B, IL-6, and TNF-α were significantly increased after thrombosis in WT mice, and enhanced by IL-17B. But IL-17B did not increase the plasma IL-6 and TNF-α in knockout mice. Conclusions. In conclusion, those results suggest that vascular endothelial necroptosis plays a crucial role in vascular injury and IL-17B could enhance the necroptosis pathway.http://dx.doi.org/10.1155/2022/6909764 |
| spellingShingle | Yunyan Li Jianfu Chen Yuan Yang Yuxue Wang Yong Zhang Yan Zhou Yan Bao Zongmei Zhang Yongping Lu Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B Journal of Immunology Research |
| title | Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B |
| title_full | Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B |
| title_fullStr | Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B |
| title_full_unstemmed | Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B |
| title_short | Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B |
| title_sort | necroptosis plays a crucial role in vascular injury during dvt and is enhanced by il 17b |
| url | http://dx.doi.org/10.1155/2022/6909764 |
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