Literature DB >> 9609762

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

S A Strong1, T T Pizarro, J S Klein, F Cominelli, C Fiocchi.   

Abstract

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-1 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.

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Year:  1998        PMID: 9609762     DOI: 10.1016/s0016-5085(98)70431-7

Source DB:  PubMed          Journal:  Gastroenterology        ISSN: 0016-5085            Impact factor:   22.682


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