Redox-sensitive regulation of macrophage-inducible nitric oxide synthase expression in vitro does not correlate with the failure of apocynin to prevent lung inflammation induced by endotoxin
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21093096
DOI
10.1016/j.imbio.2010.09.005
PII: S0171-2985(10)00160-9
Knihovny.cz E-resources
- MeSH
- Acetophenones pharmacology MeSH
- Adjuvants, Immunologic pharmacology MeSH
- Antioxidants pharmacology MeSH
- Bronchoalveolar Lavage Fluid cytology MeSH
- Cell Line MeSH
- Enzyme Inhibitors pharmacology MeSH
- Lipopolysaccharides metabolism pharmacology MeSH
- Macrophages drug effects metabolism MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- NADPH Oxidases antagonists & inhibitors MeSH
- NF-kappa B metabolism MeSH
- Nitric Oxide biosynthesis MeSH
- Oxidation-Reduction MeSH
- Pneumonia * chemically induced immunology metabolism prevention & control MeSH
- Reactive Oxygen Species metabolism MeSH
- Gene Expression Regulation, Enzymologic * drug effects MeSH
- Nitric Oxide Synthase Type II genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetophenones MeSH
- acetovanillone MeSH Browser
- Adjuvants, Immunologic MeSH
- Antioxidants MeSH
- Enzyme Inhibitors MeSH
- Lipopolysaccharides MeSH
- NADPH Oxidases MeSH
- NF-kappa B MeSH
- Nitric Oxide MeSH
- Reactive Oxygen Species MeSH
- Nitric Oxide Synthase Type II MeSH
Reactive oxygen and nitrogen species are among the crucial mediators in the development of the pathological inflammatory process in the lungs and contribute to the damage of lung epithelium. The aim of the present study was to evaluate the potential of selected antioxidants or inhibitors of NADPH oxidase (glutathione, N-acetyl cysteine, trolox, apocynin, and diphenyleneiodonium chloride) to modulate nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by mouse macrophages induced by lipopolysaccharide (LPS) in vitro and to evaluate the potential of apocynin to modulate the course of LPS-induced lung inflammation in vivo. All the tested drugs revealed inhibitory effects on LPS-induced NO production and iNOS expression in RAW 264.7 macrophages. Further, apocynin significantly inhibited activation of nuclear factor kappa B induced by LPS. Ex vivo, diphenyleneiodonium chloride and apocynin significantly reduced ROS production by inflammatory cells isolated from bronchoalveolar lavage fluid. In contrast, in vivo intranasal application of apocynin did not exert any significant effect on the course of lung inflammation in mice induced by LPS that was evaluated based on the accumulation of cells, interleukine-6, interleukine-12, RANTES, tumor necrosis factor-alpha, and protein concentration in bronchoalveolar lavage fluid and expression of iNOS in lung tissue. Only effected were the levels of nitrites 36 h after induction of lung inflammation that were reduced in the apocynin-treated group. In conclusion, our data suggest that the inhibitors of NADPH oxidase possess inhibitory potential against LPS-induced NO production by mouse macrophages; however, apocynin failed to reduce LPS-induced lung inflammation in mice.
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