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*
Division of Clinical Immunology, Mount Sinai Medical Center, New York, NY 10029; and
Department of Medicine, University of California at San Diego, Lo Jolla, CA 92093
Products of an activated immune system may affect cells within the
immune system as well as nonlymphoid cells in the local environment.
Given the immunologically activated state of the intestinal tract, it
is conceivable that locally produced cytokines could regulate
epithelial cell function. To assess whether epithelial cells are
targets for particular cytokines, we initiated studies on the binding
of a panel of proinflammatory cytokines in freshly isolated epithelial
cells from normal and inflammatory bowel disease (IBD) patients as well
as in cell lines. Isolated intestinal epithelial cells (IEC) were
stained with phycoerythrin-conjugated or biotinylated cytokines to
determine the expression and density of receptors for IL-1ß, IL-6,
granulocyte-macrophage CSF (GM-CSF), and TNF-
. Receptors for
IL-1ß, IL-6, and GM-CSF were readily detectable in all epithelial
cell preparations at levels equal to (GM-CSFR) or lower than those seen
on monocytes. However TNF
-R were not detectable on freshly isolated
IECs. Receptor density was greater in surface vs crypt epithelial
cells, but no significant differences were seen between normal and IBD
epithelial cells. Expression of IL-1R and IL-6R was enhanced by LPS and
IFN-
. Functionally, IL-1ß enhanced proliferation of the IEC cell
line, DLD1, whereas GM-CSF treatment of de-differentiated crypt-like
DLD1 and HT29 cells resulted in enhanced expression of ICAM-1.
Furthermore, TNF-
treatment enhanced the secretion of IL-8 and
GRO-
in HT29 cells, but not in freshly isolated IEC cultures.
The differential binding and function of proinflammatory cytokines on
IEC support the hypothesis that these cytokines may be involved in
normal physiological processes as well as in regulating mucosal immune
responses.
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