1. t-PA acts as a cytokine to regulate lymphocyte–endothelium adhesion in experimental autoimmune encephalomyelitis.
- Author
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Wang, Jinghua, Zhang, Xin, Mu, Lili, Zhang, Mingqing, Gao, Zhongming, Zhang, Jia, Yao, Xiuhua, Liu, Chuanliang, Wang, Guangyou, Wang, Dandan, Kong, Qingfei, Liu, Yumei, Li, Na, Sun, Bo, and Li, Hulun
- Subjects
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TISSUE plasminogen activator , *CYTOKINES , *IMMUNOREGULATION , *ENCEPHALOMYELITIS , *CELL adhesion , *VASCULAR endothelial cells , *WESTERN immunoblotting , *GENE expression - Abstract
Abstract: In this study, the capacity for t-PA to affect T cell-brain microvascular endothelial cell adhesion by acting as a cytokine was investigated. Following the treatment of a brain-derived endothelial cell line, bEnd.3, with various concentrations of t-PA, adhesion and transwell migration assays were performed. In the presence of t-PA, enhanced adhesion of T cells to bEnd.3 cells was observed. Using western blot analysis, an increase in ICAM-1 expression was detected for both t-PA-treated bEnd.3 cells and bEnd.3 cells treated with a non-enzymatic form of t-PA. In contrast, when LRP1 was blocked using a specific antibody, upregulation of ICAM-1 was inhibited and cAMP–PKA signaling was affected. Furthermore, using an EAE mouse model, administration of t-PA was associated with an increase in ICAM-1 expression by brain endothelial cells. Taken together, these findings suggest that t-PA can induce ICAM-1 expression in brain microvascular endothelial cells, and this may promote the development of EAE. [Copyright &y& Elsevier]
- Published
- 2014
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