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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3466-3469
IMMUNOBIOLOGY
Prostaglandin E2 is a selective
inducer of interleukin-12 p40 (IL-12p40) production and
an inhibitor of bioactive IL-12p70 heterodimer
Pawe Kali ski,
Pedro L. Vieira,
Joost H. N. Schuitemaker,
Esther C. de
Jong, and
Martien L. Kapsenberg
From the Department of Cell Biology and Histology and
the Department of Dermatology, Academic Medical Center, University of
Amsterdam, The Netherlands.
Interleukin-12 p70 (IL-12p70) heterodimer, composed of p35 and p40
subunits, is a major Th1-driving cytokine, promoting cell-mediated immunity. In contrast, IL-12p40 homodimer, secreted by APC in the
absence of p35 expression, and free p40 monomer do not mediate IL-12
activity but act as IL-12 antagonists. Here it is reported that
prostaglandin E2 (PGE2), an inflammatory
mediator with a previously known Th2-driving function, dose-dependently
enhances the IL-12p40 mRNA expression and the secretion of IL-12p40
protein in human tumor necrosis factor-alpha (TNF )-stimulated
immature dendritic cells (DCs). This effect is selective and is not
accompanied by the induction of IL-12p35 expression or by secretion of
IL-12p70 heterodimer. Inability of TNF/PGE2 to induce
IL-12p70 was not compensated by interferon gamma (IFN ), which
strongly enhanced the lipopolysaccharide (LPS)-induced
IL-12p70 production. In addition to the selective induction of IL-12p40
in TNF-stimulated DCs, PGE2 inhibited the production of
IL-12p70 and IL-12p40 in DCs stimulated with LPS or CD40 ligand. These
data suggest an additional level of the Th2-promoting activity of
PGE2, via selective induction of IL-12p40. Selective
induction of IL-12p40 and suppression of bioactive IL-12p70 may have
negative impact on anticancer vaccination with PGE2-matured DCs.
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