Inhibition of TNFalpha-induced cyclooxygenase-2 expression by amentoflavone through suppression of NF-kappaB activation in A549 cells.
Amentoflavone, a biflavonoid with antiinflammatory activity, downregulates COX-2 expression in TNFalpha-activatedA549 cells with concomitant inhibition of NF-kappaB mediated signaling cascades. We demonstrate here that amentoflavone inhibits NF-kappaB/ DNA binding activity potently along with inhibition of degradation of IkappaBalpha and NF-kappaB translocation into nucleus in TNFalpha-activated A549 cells. This flavonoid upregulates PPAR gamma, a transcription factor involved in repressing many cytokine-induced gene expressions. Hence amentoflavone, a dietary constituent, may be of therapeutic value for several lung diseases where COX-2 plays an important role.
D044946:Biflavonoids; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D015536:Down-Regulation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D044946:Biflavonoids; D005419:Flavonoids; D020672:I-kappa B Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C011164:amentoflavone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases