Similar to what is observed in response to ICAM-1 engagement, activation of eNOS was yet another hallmark of TFFLR, with both Ca2+ and AMPK upstream of its activation
Similar to what is observed in response to ICAM-1 engagement, activation of eNOS was yet another hallmark of TFFLR, with both Ca2+ and AMPK upstream of its activation. BBB ECs, PAR1 stimulation led to activation of signalling pathways essential to TEM; notably involving JNK and endothelial nitric oxide synthase (eNOS), with the latter downstream of AMPK. In turn, nitric oxide production through eNOS was essential for TEM by modulating VE-cadherin on Y731. Collectively, our data showed that non-canonical PAR1 activation by a lymphocyte-released serine protease is required for lymphocyte TEM across the BBB in vitro, and that this feeds into previously established Presatovir (GS-5806) ICAM-1-mediated endothelial TEM signalling pathways. < 0.05, ** < 0.01, *** < 0.001. Assays to measure lymphocyte adhesion to GPNT cells are based on radiolabel assays [7,11], which were altered for use with fluorescent cell labels as previously described [26]. Briefly, fluorescently labelled, concanavalin A (5…