Abstract
We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Apoptosis / drug effects*
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Benzamidines
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Cells, Cultured
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Culture Media
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Enzyme Activation / drug effects
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Female
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Gelatin / metabolism
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Guanidines / pharmacology*
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Humans
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Interleukin-6 / metabolism
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Lipopolysaccharides / antagonists & inhibitors*
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Lipopolysaccharides / pharmacology
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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Nitric Oxide / biosynthesis*
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Pregnancy
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Serine Proteinase Inhibitors / pharmacology*
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Trophoblasts / cytology
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Trophoblasts / drug effects*
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Trophoblasts / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Benzamidines
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Culture Media
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Guanidines
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Interleukin-6
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Lipopolysaccharides
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Serine Proteinase Inhibitors
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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Gelatin
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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nafamostat