Butein blocks tumor necrosis factor α-induced interleukin 8 and matrix metalloproteinase 7 production by inhibiting p38 kinase and osteopontin mediated signaling events in HT-29 cells

In this study, we evaluated whether butein can inhibit the effects of tumor necrosis factor α (TNF-α), an inflammatory mediator, in intestinal epithelial HT-29 cells. Butein significantly inhibited TNF-α-induced interleukin 8 (IL-8) secretion and mRNA expression. Moreover, butein suppressed the expression of matrix metalloproteinase 7 (MMP-7) mRNA and extracellular pro-MMP-7 secretion. The signal transduction study revealed that butein significantly attenuates p38 phosphorylation and inhibits osteopontin (OPN) mediated inhibitory factor κBα (I-κBα) phosphorylation in TNF-α-stimulated HT-29 cells. Using specific kinase inhibitors, we also found that blocking the p38 pathway is critical for, and blocking of OPN-mediated I-κBα phosphorylation pathway is at least for, the inhibitory effect by butein on TNF-α-induced IL-8 and MMP-7 expression. Furthermore, using an MMP inhibitor, we showed that IL-8 lies upstream of MMP-7 in the TNF-α-induced signaling process in HT-29 cells. Collectively, these results suggest that butein may be an effective agent for the treatment of intestinal inflammation.