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

Gastroenterology. 1998 Jun;114(6):1244-56. doi: 10.1016/s0016-5085(98)70431-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / physiology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • DNA / biosynthesis
  • Drug Combinations
  • Fibroblasts / metabolism
  • Gene Expression Regulation / physiology
  • Humans
  • Inflammation Mediators / physiology*
  • Interleukin-1 / pharmacology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / pharmacology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / metabolism
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • Drug Combinations
  • Inflammation Mediators
  • Interleukin-1
  • Interleukin-6
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • DNA