Dendritic Cells Issued in Vitro from Bone Marrow Produce PGE2 That Contributes to the Immunomodulation Induced by Antigen-Presenting Cells

Abstract

Given that preliminary work has indicated that prostaglandins can play a role in modulating dendritic cell (DC) functions, we addressed the prostaglandin E2 (PGE2) biosynthetic capacity of mouse DC produced in vitro from bone marrow cells. We observed production of significant amounts of PGE2, which was reduced by at least 80% when cells were incubated in the presence of indomethacin, a COX-1 preferential inhibitor. Indeed, when tested by Western blot analysis with specific COX-1 and COX-2 antibodies, only COX-1 expression could be detected in the bone marrow (BM)-DC. For lipopolysaccharide (LPS)-treated BM-DC, inhibition of PGE2 production by indomethacin or by NS-398 (a COX-2-selective inhibitor) used alone was less potent. After LPS treatment of BM-DC, COX-1 and COX-2 expression was potent, and inhibition of PGE2 synthesis needed the presence of both indomethacin and NS-398. We also observed that exogenous PGE2 diminished the expression of MHC class II molecules by BM-DC and that prostaglandin and indomethacin had antagonistic effects on cell proliferation during the mixed lymphocyte reaction using BM-DC as stimulatory cells. This assessment of PGE2 suggests that endogenous PGE2 produced by DC might play a role as an immunomodulating factor during the immune response. This hypothesis is sustained by the fact that IL-12 production by BM-DC is modulated by exogenous PGE2 as well as endogenous prostaglandin, since either the addition of exogenous PGE2 or the presence of LPS (which increases endogenous PGE2 synthesis) decreases IL-12 production, while NS-398 (which decreases LPS-induced PGE2 synthesis) increases IL-12 synthesis.