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Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan
PGE2 has been known to suppress Th1 responses. We
studied the role of PGE2 in two representative chemokines,
macrophage-derived chemokine (MDC) and IFN-inducible protein-10,
production by LPS- or CD40-stimulated spleen cells. The production of
MDC, one of the ligands for CCR4 preferentially expressed on Th2, was
enhanced in nonstimulated, LPS-, CD40-, or CD3-stimulated spleen cells
by the pretreatment with PGE2, while the production of
IFN-inducible protein-10, a representative ligand for CXC chemokine
receptor 3 expressed on Th1, was suppressed. MDC production was also
enhanced by IL-4, IL-5, and intracellular cAMP-elevating agents such as
dibutyryl cAMP and 3-isobutyl-1-methylxanthine, and the effect of IL-4,
IL-5, and PGE2 was additive. However, the pretreatment with
IL-6, IL-10, or TGF-
, or the neutralization of IFN-
or IL-12 had
no effect on MDC production. B cells, macrophages, and dendritic cells
were main producers of MDC, while T cells produced only a small amount
of MDC. MDC production by B cells was equally stimulated by LPS and
anti-CD40 Ab, while that by macrophages and dendritic cells was
more markedly stimulated by anti-CD40 Ab, and PGE2
further enhanced MDC production by these stimulated cells. These
results indicate that PGE2 regulates Th1/Th2-related
chemokine production by B cells, macrophages, and dendritic cells, and
that this is a new function of PGE2 for the regulation of
Th2 immune responses at the induction and activation
stages.
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