Differential effects of IL-10 on prostaglandin H synthase-2 expression and prostaglandin E2 biosynthesis between spleen and bone marrow macrophages

Different populations of mononuclear phagocytes (MO) show considerable diversity of cellular function including prostaglandin E-2 (PGE(2)) biosynthesis. Certain bacterial components enhance PGE2 biosynthesis differentially in selected populations of MO. Interleukin (IL)-10 is proposed to inhibit modulation of PGE(2) biosynthesis by down-regulating prostaglandin G/H synthase-2 (PGHS-2) expression. To assess whether IL-10 regulates PGE2 biosynthesis and PGHS-2 expression, splenic and bone marrow MO were isolated from IL-10-deficient (IL-10(-/-)), C57B1/6 [wild-type (WT) control], and Balb/c (comparison control) mice and were treated with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma) as a model of bacterial inflammation. LPS-induced PGHS-2 expression was similar for splenic MO isolated from the three strains of mice. However, PGE(2) released by LPS-treated splenic MO was significantly higher in IL-10-/- and Balb/c than in WT cells. In the presence of LPS and IFN-gamma, PGHS-2 expression and PGE(2) release by IL-10(-/-) and Balb/c splenic MO were enhanced compared with stimulation with LPS alone or IFN-gamma alone. However, there was no significant increase in PGE2 release from WT splenic MO treated with LPS plus IFN-gamma despite increased PGHS-2 expression. In sharp contrast, PGHS-2 expression and PGE(2) release by bone marrow MO were greatly enhanced in IL-10-/- cells compared with control cells. Our results indicate that IL-10 regulation of MO PGE(2) biosynthesis and PGHS-2 expression is compartment-dependent and that PGE(2) production is not linked directly to PGHS-2 levels. Furthermore, our findings emphasize strain-specific differences between C57B1/6 and Balb/c mice, and Balb/c appears more similar to the IL-10-/- than to the C57B1/6 with respect to prostanoid production.