期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 3, 期 9, 页码 1335-1344出版社
ELSEVIER
DOI: 10.1016/S1567-5769(03)00146-2
关键词
I kappa B; lipopolysaccharide; macrophages; NF-kappa B; nitric oxide; protease inhibitor
Nafamostat mesilate (NM), a clinically used serine protease inhibitor, Suppressed the overproduction of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in RAW264.7 murine macrophages treated with lipopolysaccharide (LPS, 100 ng/ml); however, it had little effect oil endothelial NOS (eNOS) in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assay (EMSA) revealed that LPS activated nuclear factor-kappaB (NF-kappaB) in RAW264.7 cells and that this activation was suppressed by nafamostat mesilate. Western blotting showed that nafamostat mesilate suppressed the phosphorylation and degradation of inhibitor kappaB-alpha (IkappaB-alpha), which holds NF-kappaB in the cytoplasm in an inactivated state. Our observations suggest that nafamostat mesilate is a candidate agent for various diseases such as ischemia-reperfusion, graft rejection, inflammatory diseases, and autoimmune diseases, in which iNOS and/or NF-kappaB are upregulated. (C) 2003 Elsevier B.V. All rights reserved.
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