title: Proinflammatory cytokines differentially modulate their own expression in human intestinal mucosal mesenchymal cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic Foundation, Ohio, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Strong
authors.forename: T T
authors.initials: TT
authors.lastname: Pizarro
authors.forename: J S
authors.initials: JS
authors.lastname: Klein
authors.forename: F
authors.initials: F
authors.lastname: Cominelli
authors.forename: C
authors.initials: C
authors.lastname: Fiocchi
mesh_terms: D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D004338:Drug Combinations; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA