ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action
- Authors
- Lee, Jeong-Oog; Jeong, Deok; Kim, Mi-Yeon; Cho, Jae Youl
- Issue Date
- 2015
- Publisher
- HINDAWI PUBLISHING CORP
- Citation
- MEDIATORS OF INFLAMMATION
- Journal Title
- MEDIATORS OF INFLAMMATION
- URI
- http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/9827
- DOI
- 10.1155/2015/967053
- ISSN
- 0962-9351
- Abstract
- Luteolin is a flavonoid identified as a major anti-inflammatory component of Artemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin from Artemisia asiatica was examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor( TNF-)-alpha, and cyclooxygenase-2 (COX-2) in lipopolysaccharide-(LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-kappa B (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-kappa B signaling cascade via blockade of ATP binding in Src and Syk.
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