UNCORRECTED PROOF 1 t-PA acts as a cytokine to regulate 2 lymphocyte-endothelium adhesion in 3 experimental autoimmune encephalomyelitis

Q2 In this study, the capacity for t-PA to affect T cell-brain microvascular endothelial 26 cell adhesion by acting as a cytokine was investigated. Following the treatment of a 27 brain-derived endothelial cell line, bEnd.3, with various concentrations of t-PA, adhesion and 28 transwell migration assays were performed. In the presence of t-PA, enhanced adhesion of T 29 cells to bEnd.3 cells was observed. Using western blot analysis, an increase in ICAM-1 expression 30 was detected for both t-PA-treated bEnd.3 cells and bEnd.3 cells treated with a non-enzymatic 31 form of t-PA. In contrast, when LRP1 was blocked using a specific antibody, upregulation of 32 ICAM-1 was inhibited and cAMP–PKA signaling was affected. Furthermore, using an EAE mouse