TY - JOUR
T1 - Nafamostat mesilate suppresses NF-κB activation and NO overproduction in LPS-treated macrophages
AU - Noguchi, Soichi
AU - Nakatsuka, Mikiya
AU - Konishi, Hideki
AU - Kamada, Yasuhiko
AU - Chekir, Chebib
AU - Kudo, Takafumi
N1 - Funding Information:
A part of this work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, from the JAOG Ogyaa Donation Foundation, and from Kanzawa Medical Research Foundation.
PY - 2003/9
Y1 - 2003/9
N2 - 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.
AB - 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.
KW - IκB
KW - Lipopolysaccharide
KW - Macrophages
KW - NF-κB
KW - Nitric oxide
KW - Protease inhibitor
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U2 - 10.1016/S1567-5769(03)00146-2
DO - 10.1016/S1567-5769(03)00146-2
M3 - Article
C2 - 12890431
AN - SCOPUS:0042199066
SN - 1567-5769
VL - 3
SP - 1335
EP - 1344
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 9
ER -
