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

Mikiya Nakatsuka, Kazuo Asagiri, Soichi Noguchi, Toshihiro Habara, Takafumi Kudo

Research output: Contribution to journalArticle

42 Citations (Scopus)

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. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1243-1250
Number of pages8
JournalLife Sciences
Volume67
Issue number10
DOIs
Publication statusPublished - Jul 28 2000

Keywords

  • Apoptosis
  • Lipopolysaccharide
  • Matrix metalloproteinases
  • Nafamostat mesilate
  • Nitric oxide
  • Peroxynitrite
  • Protease inhibitor
  • Trophoblasts

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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