Caco-2 cocultured with THP-1, time course

Previously, we constructed a coculture model to analyze the effect of macrophages on intestinal epithelial cells, and found that TNF-a secreted from human macrophage-like THP-1 cells induced cell damage to intestinal epithelial Caco-2 cells (Exp.Cell.Res. 2006, 312(19):3909-19). In this study, we present activation of NF-kB in Caco-2 cells within 15 min after coculturing. To reveal how TNF-a secreted from THP-1 cells affects Caco-2 cells in an early stage of coculture, we exhaustively analyzed the changes of gene expression in Caco-2 cells cocultured with THP-1 cells over the time periods of 0, 1, 3, 6, 24, and 48 h by using a DNA microarray. Differentially expressed genes extracted with maSigPro demonstrated that IEX-1 was the lowest p-value gene, that is, the most significantly changed gene among the up-regulated genes. The genes expressed in a similar pattern to IEX-1 involved immunity, apoptosis, and protein kinase cascade. These findings suggest that the stimuli of TNF-a from THP-1 cells activates NF-kB, leading induction of various gene expression. This pattern of gene expression indicates that not only early defense response but also cell death occurs at the same time, causing inflammatory condition.

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Ishimoto Y, Nakai Y, Satsu H, Totsuka M, Shimizu M