Dendritic cells issued in vitro from bone marrow produce PGE(2) that contributes to the immunomodulation induced by antigen-presenting cells

Given that preliminary work has indicated that prostaglandins can play a ro le in modulating dendritic cell (DC) functions, we addressed the prostaglan din E, (PGE,) biosynthetic capacity of mouse DC produced in vitro from bone marrow cells. We observed production of significant amounts of PGE(2), whi ch was reduced by at least 80% when cells were incubated in the presence of indomethacin, a COX-1 preferential inhibitor. Indeed, when tested by Weste rn blot analysis with specific COX-1 and COX-2 antibodies, only COX-1 expre ssion could be detected in the bone marrow (BM)-DC, For lipopolysaccharide (LPS)-treated BM-DC, inhibition of PGE(2) production by indomethacin or by NS-398 (a COX-9-selective inhibitor) used alone was less potent, After LPS treatment of BM-DC, COX-1 and COX-2 expression was potent, and inhibition o f PGE(2) synthesis needed the presence of both indomethacin and NS-398, We also observed that exogenous PGE(2) diminished the expression of MHC class II molecules by BM-DC and that prostaglandin and indomethacin had antagonis tic effects on cell proliferation during the mixed lymphocyte reaction usin g BM-DC as stimulatory cells. This assessment of PGE(2) suggests that endog enous PGE(2) 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 PGE, as well as endogen ous prostaglandin, since either the addition of exogenous PGE(2) or the pre sence of LPS (which increases endogenous PGE, synthesis) decreases IL-12 pr oduction, while NS-398 (which decreases LPS-induced PGE(2) synthesis) incre ases IL-12 synthesis. (C) 2001Academic Press.