Urinary trypsin inhibitor reduces LPS- induced hypotension by suppressing tumor necrosis factor-alpha production through inhibition of Egr-1 expression.
Although urinary trypsin inhibitor (UTI) has been shown to inhibit tumor necrosis factor (TNF)-alpha- 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-alpha 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 i.v.) inhibited LPS (5 mg/kg i.v.)- induced increases in lung tissue levels of Egr-1, TNF-alpha mRNA, and TNF-alpha in rats. UTI inhibited LPS-induced hypotension by inhibiting pulmonary induction of inducible nitric oxide synthase ( iNOS). We previously demonstrated that anti- TNF-alpha 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-alpha 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.[1]References
- Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-alpha production through inhibition of Egr-1 expression. Molor-Erdene, P., Okajima, K., Isobe, H., Uchiba, M., Harada, N., Okabe, H. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg