{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T23:05:53Z","timestamp":1784156753358,"version":"3.55.0"},"reference-count":31,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,4,1]]},"abstract":"<jats:p>Thrombin-stimulated endothelium synthesizes numerous adhesion molecules to recruit leukocytes; however, it is unknown which intracellular pathways are responsible for this event. A recent report from our laboratory has shown that thrombin induces E-selectin expression and that blocking nuclear factor-\u03baB (NF-\u03baB) activity partially blocked both E-selectin expression (60%) and leukocyte recruitment. In this study, we systematically assessed the importance of p38 MAPK in thrombin-induced NF-\u03baB activation and E-selectin-dependent leukocyte recruitment. Thrombin caused phosphorylation of p38 MAPK, its substrate ATF-2, and JNK MAPK, but not ERK MAPK. The p38 MAPK inhibitors, SKF86002 and SB-203580 only reduced ATF-2 activity. We treated human umbilical vein endothelial cells with SKF86002, 1 h before thrombin stimulation, and noted inhibition of NF-\u03baB mobilization and complete inhibition of leukocyte rolling and adhesion in a laminar flow chamber. Significant inhibition of leukocyte recruitment and E-selectin expression was also observed with SB-203580. SKF86002 did not affect other systems, including tumor necrosis factor-\u03b1-induced E-selectin-dependent leukocyte recruitment. Moreover, thrombin-induced rapid mobilization of P-selectin from Weibel Palade bodies was not p38 MAPK dependent. These data suggest that thrombin induces p38 MAPK activation, which leads to NF-\u03baB mobilization to the nucleus and causes the upregulation of E-selectin and subsequent leukocyte recruitment.<\/jats:p>","DOI":"10.1152\/ajpheart.00016.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:08:56Z","timestamp":1425413336000},"page":"H1095-H1103","source":"Crossref","is-referenced-by-count":29,"title":["P38 MAPK: critical molecule in thrombin-induced NF-\u03baB-dependent leukocyte recruitment"],"prefix":"10.1152","volume":"284","author":[{"given":"Jaswinder","family":"Kaur","sequence":"first","affiliation":[{"name":"Immunology Research Group, Departments of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Woodman","sequence":"additional","affiliation":[{"name":"Immunology Research Group, Departments of Physiology and 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