IFN-gamma-induced iNOS mRNA expression is inhibited by rebamipide in murine macrophage RAW264.7 cells.
To investigate the effects of rebamipide, an antigastritis and anti-gastric ulcer drug, on inducible nitric oxide synthase (iNOS), murine macrophage RAW264.7 cells were treated with interferon-gamma (IFN-gamma) in the presence of rebamipide. NO production was stimulated by IFN-gamma, and the level was attenuated by rebamipide in a dose-dependent manner. Therefore, we investigated the possibility that either rebamipide directly inhibited iNOS enzyme activity or that it reduced iNOS mRNA expression. In a cell-free system, rebamipide did not affect iNOS enzyme activity; however, rebamipide inhibited iNOS mRNA and protein expression induced by IFN-gamma. Thus, we concluded that rebamipide inhibited IFN-gamma-induced NO production as a result of its inhibitory action on iNOS mRNA expression.
Nagano
C
C
Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.
Wakebe
H
H
Azuma
A
A
Imagawa
K
K
Kikuchi
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D000975:Antioxidants; D015363:Quinolones; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C052785:rebamipide; D000409:Alanine