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

doi:10.1016/S0024-3205(00)00716-5

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 journal › Article › peer-review

43 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 language	English
Pages (from-to)	1243-1250
Number of pages	8
Journal	Life Sciences
Volume	67
Issue number	10
DOIs	https://doi.org/10.1016/S0024-3205(00)00716-5
Publication status	Published - 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)

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts. / Nakatsuka, Mikiya; Asagiri, Kazuo; Noguchi, Soichi; Habara, Toshihiro; Kudo, Takafumi.

In: Life Sciences, Vol. 67, No. 10, 28.07.2000, p. 1243-1250.

Research output: Contribution to journal › Article › peer-review

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

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.",

keywords = "Apoptosis, Lipopolysaccharide, Matrix metalloproteinases, Nafamostat mesilate, Nitric oxide, Peroxynitrite, Protease inhibitor, Trophoblasts",

author = "Mikiya Nakatsuka and Kazuo Asagiri and Soichi Noguchi and Toshihiro Habara and Takafumi Kudo",

note = "Funding Information: A part of this work was supported by a Grant-in-Aid for Scienti{\TH}c Research from the Ministry of Education, Science and Culture of Japan (No. 09771278) and from the JAOG Ogyaa Donation Foundation.",

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AU - Asagiri, Kazuo

AU - Noguchi, Soichi

AU - Habara, Toshihiro

AU - Kudo, Takafumi

N1 - Funding Information: A part of this work was supported by a Grant-in-Aid for ScientiÞc Research from the Ministry of Education, Science and Culture of Japan (No. 09771278) and from the JAOG Ogyaa Donation Foundation.

PY - 2000/7/28

Y1 - 2000/7/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Lipopolysaccharide

KW - Matrix metalloproteinases

KW - Nafamostat mesilate

KW - Nitric oxide

KW - Peroxynitrite

KW - Protease inhibitor

KW - Trophoblasts

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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