Inhibitory effect of luteolin on TNF-α-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 IκB degradation and NF-κB activation. In this study, we investigated the role of luteolin, a major flavonoid of Lonicera japonica, on TNF-α-induced IL-8 production in human colonic epithelial cells. HT29 cells were stimulated with TNF-α 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 IκB degradation were determined by Western blot analysis. NF-κB activation was assessed by the electrophoretic motility shift assay (EMSA). Luteolin suppressed TNF-α-induced IL-8 production in dose-dependent manner. In addition, luteolin inhibited TNF-α-induced phosphorylation of p38 MAPK and extracellular-regulated kinases (ERK), IκB degradation, and NF-κB activation. These results suggest that luteolin has the inhibitory effects on TNF-α-induced IL-8 production in the intestinal epithelial cells through blockade in the phosphorylation of MAPKs, following IκB degradation and NF-κB activation.