Bile acids inhibit tumour necrosis factor alpha-induced interleukin-8 production in human colon epithelial cells

To clarify the regulatory mechanism of the production of various inflammatory mediators by intestinal epithelial cells, the effect of bile acids (tauroursodeoxycholate, TUDC; taurochenodeoxycholate, TCDC; and taurocholate, TC) on the cytokine-induced production of interleukin (IL)-8 in a human colon epithelial cell line (HT-29) was examined. HT-29 cells were incubated for 24 h in a culture medium containing tumour necrosis factor alpha (TNF alpha; 1 ng/mL) and/or interleukin (IL)-1beta (1 ng/mL) in the presence or absence of bile acids. The IL-8 concentration in the medium was measured by an enzyme-linked immunosorbent assay. The binding assay of TNF alpha was performed using [125I]-TNF alpha (100 pmol/L). Interleukin-8 production during incubation with TNF alpha was markedly reduced in the presence of 0.5 and 1 mmol/LTUDC, 0.5 and 1 mmol/LTCDC and 0.5 and 1 mmol/LTC, by 56, 85, 86, 91, 37 and 70%, respectively. The IL-8 production during incubation with IL-1beta was not significantly reduced in the presence of these bile acids. The specific binding of TNF alpha to cells was inhibited 33, 47, and 14% by 1 mmol/LTUDC, TCDC and TC, respectively. These findings suggest that bile acids inhibit TNF alpha-induced IL-8 production by the colonic cells. The suppression may be partly due to inhibition of TNF alpha binding to the cells by bile acids.