Proinflammatory cytokines differentially modulate their own expression in human intestinal mucosal mesenchymal cells

Background & Aims: Intestinal homeostasis is coordinated through the response of different cell types, including the interaction of immune with nonimmune cells. This study investigated the effect of immune cell-derived proinflammatory cytokines on mesenchymal cell proliferation and gene product expression. Methods: Primary cultures of human mucosal mesenchymal cells were activated with interleukin (Il)-1 beta, IL-6, and tumor necrosis factor alpha. (TNF-alpha). Proliferation was measured by thymidine incorporation, messenger RNA (mRNA) expression was assessed by Northern blot analysis, and IL-l receptor type was identified by reverse-transcription polymerase chain reaction. Results: Mesenchymal cells dose-dependently proliferated in response to IL-1 beta, IL-6, and TNF-alpha. Each cytokine differentially induced mRNA expression in a dose-dependent and selective fashion: IL-1 beta was the most potent inducer, TNF-alpha was weaker, and IL-6 induced little or no mRNA; in contrast, IL-6 mRNA was the most abundantly induced, followed by IL-1 beta mRNA, whereas TNF-alpha mRNA was weakly and infrequently expressed. The IL-1 receptor antagonist inhibited cytokine mRNA expression, and mesenchymal cells expressed the type II, but not the type I, IL-1 receptor. Conclusions: The ability of intestinal mesenchymal cells to express proinflammatory gene products implicates them as regulators of local immune cells through immune-nonimmune interactions. Thus, mesenchymal cells should be considered as active regulators of intestinal immunity under normal and inflammatory conditions.