Proinflammatory cytokines differentially modulate their own expression in human intestinal mucosal mesenchymal cells.
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.
Strong
S A
SA
Department of Colorectal Surgery, Cleveland Clinic Foundation, Ohio, USA.
Pizarro
T T
TT
Klein
J S
JS
Cominelli
F
F
Fiocchi
C
C
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
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