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Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
67
Issue
10
Identifiers
DOI: 10.1016/s0024-3205(00)00716-5
Keywords
  • Apoptosis
  • Lipopolysaccharide
  • Matrix Metalloproteinases
  • Nafamostat Mesilate
  • Nitric Oxide
  • Peroxynitrite
  • Protease Inhibitor
  • Trophoblasts
Disciplines
  • Biology
  • Medicine

Abstract

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.

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