{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:49:30Z","timestamp":1761540570642},"reference-count":31,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p>Although urinary trypsin inhibitor (UTI) has been shown to inhibit tumor necrosis factor (TNF)-\u03b1- production, the detailed mechanism(s) remains unclear. This study was undertaken to elucidate the molecular mechanism(s) underlying this inhibitory effect in monocytes in vitro and in rats given lipopolysaccharide (LPS). TNF-\u03b1 production by monocytes stimulated with LPS (100 ng\/ml) was inhibited by UTI at concentrations higher than 100 U\/ml. Expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinases 1\/2 in monocytes stimulated with LPS were inhibited by UTI. UTI (50,000 U\/kg iv) inhibited LPS (5 mg\/kg iv)-induced increases in lung tissue levels of Egr-1, TNF-\u03b1 mRNA, and TNF-\u03b1 in rats. UTI inhibited LPS-induced hypotension by inhibiting pulmonary induction of inducible nitric oxide synthase (iNOS). We previously demonstrated that anti-TNF-\u03b1 antibody and aminoguanidine, a selective inhibitor of iNOS, reduced LPS-induced hypotension in this animal model. Furthermore, we also reported that reduction of LPS-induced coagulation abnormalities in rats did not affect inflammatory responses and hypotension in this animal model. Taken together, these observations strongly suggested that UTI inhibited LPS-induced production of TNF-\u03b1 by inhibiting activation of the extracellular signal-regulated protein kinases 1\/2-Egr-1 pathway in monocytes, which might at least partly contribute to reduction of hypotension through inhibition of iNOS induction in rats given LPS.<\/jats:p>","DOI":"10.1152\/ajpheart.00885.2004","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T01:13:58Z","timestamp":1100222038000},"page":"H1265-H1271","source":"Crossref","is-referenced-by-count":27,"title":["Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-\u03b1 production through inhibition of Egr-1 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