Inhibitory effect of luteolin on TNF-alpha-induced IL-8 production in human colon epithelial cells.
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.
Kim
Jin-A
JA
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 570-749, South Korea.
Kim
Dae-Ki
DK
Kang
Ok-Hwa
OH
Choi
Yeon-A
YA
Park
Hye-Jung
HJ
Choi
Suck-Chei
SC
Kim
Tae-Hyun
TH
Yun
Ki-Jung
KJ
Nah
Yong-Ho
YH
Lee
Young-Mi
YM
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
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