Nafamostat mesilate suppresses NF-κB activation and NO overproduction in LPS-treated macrophages

Soichi Noguchi, Mikiya Nakatsuka, Hideki Konishi, Yasuhiko Kamada, Chebib Chekir, Takafumi Kudo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 on endothelial NOS (eNOS) in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assay (EMSA) revealed that LPS activated nuclear factor-κB (NF-κB) 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 κB-α (IκB-α), which holds NF-κB 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-κB are upregulated.

Original languageEnglish
Pages (from-to)1335-1344
Number of pages10
JournalInternational Immunopharmacology
Volume3
Issue number9
DOIs
Publication statusPublished - Sep 2003

Keywords

  • IκB
  • Lipopolysaccharide
  • Macrophages
  • NF-κB
  • Nitric oxide
  • Protease inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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