Effect of flavone derivatives on interleukin-1beta (IL-1beta) mRNA expression and IL-1beta protein synthesis in stimulated RAW 264.7 macrophages.
It is known that the redox status of cells affects gene expression. Flavones, as natural antioxidants, efficiently modulate this status and may play a role in the regulation of inducible gene expression of inflammatory mediators. This study was designed to investigate the effect of five flavone derivatives variously substituted with hydroxyl groups (chrysin, galangin, kaempferol, quercetin and myricetin) on interleukin-1beta (IL-1beta) gene expression in stimulated RAW 264.7 macrophages. The cells were incubated with tested hydroxyflavones and stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Then, the following were estimated: the level of IL-1beta mRNA in these cells and the concentration of IL-1beta protein in cell-culture supernatants and cell lysates. Each of the tested compounds significantly decreased IL-1beta mRNA expression. The most potent inhibitor was chrysin (hydroxyflavone with two hydroxyl groups and a weak antioxidant activity). The effects of galangin and kaempferol were similar. Myricetin (hydroxyflavone with a strong antioxidant activity) significantly decreased the level of IL-1beta mRNA, but it had no effect on the IL-1beta protein synthesis. The results indicated that hydroxyflavones could modulate the IL-1beta gene expression in activated RAW 264.7 macrophages via inhibiting gene transcription. This action seems unlikely to be the result of antioxidant properties of tested compounds.
Blonska
M
M
Department of Microbiology and Immunology, Medical University of Silesia, Zabrze-Rokitnica, Poland.
Czuba
Z P
ZP
Krol
W
W
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D005419:Flavonoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase