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• W2021509170 abstract "The procoagulant thrombin stimulates endothelial cells (EC) to undergo rapid cytoskeleton changes via signaling pathways that induce multiple phenotypic changes, including alterations in permeability, vasomotor tone, adhesion molecule synthesis, and leukocyte trafficking. We studied a novel role of thrombin's action on the endothelium that results in MIF secretion, which is linked to myosin light chain (MLC) and extracellular signal-regulated kinase (ERK½)-dependent nuclear signaling. In bovine pulmonary artery EC (BPAEC), thrombin treatment induced intracellular MLC phosphorylation within 15 min, followed by a significant increase in MIF secretion within 30 min. Thrombin treatment induced biphasic ERK½ phosphorylation with an early phase occurring at 15 min and a later phase at 120 min. To understand the role of MIF secretion in thrombin-induced biphasic activation of ERK½, BPAE cells were treated with (i) recombinant MIF, and (ii) the medium collected from thrombin-treated BPAE cells. These studies demonstrated a sustained monophasic ERK½ phosphorylation. Inhibition of MIF secretion by MIF siRNA or antisense-MIF treatment, along with a neutralizing antibody, attenuated the thrombin-induced second phase ERK phosphorylation, suggesting a direct involvement of MIF in the second phase of ERK½ activation. Pretreatment of BPAE cells with an ERK kinase inhibitor and with antisense-MIF significantly inhibited thrombin-induced nuclear factor kappa (NF-κB) activation. These results indicate that MIF secretion and ERK phosphorylation both play a necessary role in thrombin induced NF-κB activation. J. Cell. Biochem. 105: 1279–1288, 2008. © 2008 Wiley-Liss, Inc." @default.
• W2021509170 created "2016-06-24" @default.
• W2021509170 creator A5018740104 @default.
• W2021509170 creator A5052491243 @default.
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• W2021509170 date "2008-12-01" @default.
• W2021509170 modified "2023-09-26" @default.
• W2021509170 title "Thrombin induced secretion of macrophage migration inhibitory factor (MIF) and its effect on nuclear signaling in endothelium" @default.
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• W2021509170 doi "https://doi.org/10.1002/jcb.21928" @default.
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