title: Inhibitory effect of luteolin on TNF-alpha-induced IL-8 production in human colon epithelial cells.
abstract: Interleukin (IL)-8 plays a central role in the initiation and maintenance of inflammatory responses in the inflammatory bowel disease. The proinflammatory cytokine-mediated production of IL-8 requires activation of various kinases, which leads to the IkappaB degradation and NF-kappaB activation. In this study, we investigated the role of luteolin, a major flavonoid of Lonicera japonica, on TNF-alpha-induced IL-8 production in human colonic epithelial cells. HT29 cells were stimulated with TNF-alpha in the presence or absence of luteolin. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and the mitogen-activated protein kinases (MAPKs) activation and IkappaB degradation were determined by Western blot analysis. NF-kappaB activation was assessed by the electrophoretic motility shift assay (EMSA). Luteolin suppressed TNF-alpha-induced IL-8 production in dose-dependent manner. In addition, luteolin inhibited TNF-alpha-induced phosphorylation of p38 MAPK and extracellular-regulated kinases (ERK), IkappaB degradation, and NF-kappaB activation. These results suggest that luteolin has the inhibitory effects on TNF-alpha-induced IL-8 production in the intestinal epithelial cells through blockade in the phosphorylation of MAPKs, following IkappaB degradation and NF-kappaB activation.
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749, South Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Kim
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Kim
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kang
authors.forename: Yeon-A
authors.initials: YA
authors.lastname: Choi
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Suck-Chei
authors.initials: SC
authors.lastname: Choi
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.forename: Ki-Jung
authors.initials: KJ
authors.lastname: Yun
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Nah
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D047311:Luteolin