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-Chain1
Departments of
*
Surgery and
Microbiology, University of Mississippi Medical Center, Jackson, MS 39216
NK cell function is regulated by cytokines and certain biochemical
mediators in a positive or negative manner. This study was performed to
investigate the suppressive effects of PGE2 on
IL-15-activated human NK cell function. Purified NK cells were cultured
with 200 ng/ml IL-15 for 2 days in the presence or absence of 10–200
ng/ml PGE2. PGE2 significantly suppressed NK
cell-mediated cytotoxicity and IFN-
production at the secretional
and the transcriptional levels. We also evaluated the effect of
PGE2 on the IL-15R complex that consists of IL-2R
,
common -chain (c-chain), and a specific chain
IL-15R
. Percentage of positive cells and number of binding sites for
c-chain were significantly increased after IL-15
treatment; however, a substantial decrease was observed with
PGE2 cotreatment. In contrast, constitutive expression of
IL-2R was significantly decreased after IL-15 treatment, with no
change detected in the presence of PGE2. At the
transcriptional level, neither IL-15 nor PGE2 had
significant effects on the expression of - or
c-chains. There was a 3-fold increase in the expression
of IL-15R at the transcriptional level that peaked at 8 h after
IL-15 treatment; however, PGE2 had no significant effect.
Suppression of NK function by PGE2 was not due to the
endogenous production of IL-4, IL-10, or TGF-1 by NK
cells. These results suggest that down-regulation of surface expression
of c-chain on NK cells may be one mechanism through
which PGE2 mediates suppression of IL-15-activated NK cell
function.
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