The effect of cytokines on the taurine uptake by human intestinal epithelial Caco-2 cells was investigated. Among the various cytokines tested, tumor necrosis factor K K (TNF-K K) markedly increased the taurine uptake by Caco-2 cells, resulting in an increase in the intracellular taurine level. TNF-K K did not induce up-regulation of the taurine uptake in hepatic HepG2, renal human embryo kidney 293, and macrophage-like THP-1 cells. The uptake of glycine, L-leucine, and L-glutamic acid by Caco-2 cells was not affected by TNF-K K. A kinetic analysis of the taurine uptake by TNF-K K-treated Caco-2 cells suggests that this up-regulation was associated with both an increase in the amount of the taurine transporter (TAUT) and an increase in its affinity. TNF-K K-treated cells showed a higher mRNA level of the TAUT than did the control cells. ß
Immune cells located in the intestinal epithelium interact with intestinal epithelial cells via soluble factors. In this study, a new in vitro model using a coculture system was constructed to analyze the interaction between intestinal epithelial cells and macrophage-like cells. Human intestinal epithelial Caco-2 cells were differentiated on semipermeable membranes. Human monocytic THP-1 cells were differentiated to macrophage-like cells and then cocultured on the basolateral side of the Caco-2 cell monolayers. By coculturing for 48 hours, an increased release of lactate dehydrogenase from the Caco-2 cells and a decrease in the transepithelial electrical resistance of the monolayers were observed, suggesting that the coculture with THP-1 induced some disruption of the Caco-2 cells. This disruption was significantly suppressed by adding the anti-TNF-alpha antibody to the medium, suggesting that TNF-alpha secreted from THP-1 caused damage to the Caco-2 cells. It is also suggested that this phenomenon is similar to that observed with inflammatory bowel disease (IBD). The effects of food factors on the cells in this coculture system were examined. The disruption of the Caco-2 cell monolayers was significantly reduced by adding caffeine to the medium on the apical side. It is hoped that this coculture system will be a good model for the treatment of IBD.
We have previously demonstrated that the taurine uptake and transporter (TAUT) mRNA expression were upregulated by tumor necrosis factor a (TNF-a) in Caco-2 cells. In this present study, the signaling molecules related to this upregulation were investigated. Pyrrolidine dithiocarbamate, a nuclear factor jB (NF-jB) inhibitor, repressed the upregulation of taurine uptake and TAUT mRNA expression. A reporter assay revealed that TNF-a-induced TAUT transcriptional activity through the NF-jB consensus-like sequence in the human TAUT promoter region. An electrophoretic mobility shift assay showed that NF-jB could bind to the NF-jB consensus-like sequence. The anti-TNF receptor 1 (TNFR1) antibody, but not the TNF receptor 2 (TNFR2) antibody, repressed this upregulation.
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