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

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

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Background and 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)-1β, IL-6, and tumor necrosis factor α (TNF- α). 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- 1β, IL-6, and TNF-α. Each cytokine differentially induced mRNA expression in a dose-dependent and selective fashion: IL-1β was the most potent inducer, TNF-α was weaker, and IL-6 induced little or no mRNA; in contrast, IL-6 mRNA was the most abundantly induced, followed by IL-1β mRNA, whereas TNF-α 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.

Original languageEnglish (US)
Pages (from-to)1244-1256
Number of pages13
JournalGastroenterology
Volume114
Issue number6
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Gastroenterology

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