Luteolin inhibits the nuclear factor-kappa B transcriptional activity in Rat-1 fibroblasts.
Flavonoids are natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we investigated the effects of several flavonoids on nuclear factor-kappa B (NF-kappa B) activation by using luciferase reporter gene assay. Among the flavonoids examined, luteolin showed the most potent inhibition on lipopolysaccharide (LPS)-stimulated NF-kappa B transcriptional activity in Rat-1 fibroblasts. Luteolin did not inhibit either I kappa B alpha degradation or NF-kappa B nuclear translocation, DNA binding or phosphorylation by LPS. However, luteolin prevented LPS-stimulated interaction between the p65 subunit of NF-kappa B and the transcriptional coactivator CBP. In addition, a specific PKA inhibitor that blocked the phosphorylation of CREB and c-Jun by luteolin partially reversed the inhibitory effect of luteolin on NF-kappa B.CBP complex formation and NF-kappa B transcriptional activity by LPS. These data imply that inhibition of NF-kappa B transcriptional activity by luteolin may occur through competition with transcription factors for coactivator that is available in limited amounts. Taken together, this study provides a molecular basis for the understanding of the anti-inflammatory effects of luteolin.
Kim
Sun-Hee
SH
Department of Life Science, Division of Molecular and Life Science and School of Environmental Science and Engineering, Pohang University of Science and Technology, San 31 Hyojadong, Nam-Gu, Pohang, Kyungbuk 790-784, South Korea.
Shin
Kum-Joo
KJ
Kim
Dohan
D
Kim
Yun-Hee
YH
Han
Myoung-Sook
MS
Lee
Taehoon-G
TG
Kim
Euikyung
E
Ryu
Sung-Ho
SH
Suh
Pann-Ghill
PG
D051697:Activating Transcription Factor 1; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology; D047311:Luteolin; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D005419:Flavonoids; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D047311:Luteolin