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Published online before print January 18, 2005
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* Department of Biomedical Sciences, Florida Atlantic University, Boca Raton;
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, North Carolina; and
Myrvik Enterprises, Southport, North Carolina
1 Correspondence: Department of Biomedical Sciences, Florida Atlantic University, 777 Glades Rd., P.O. Box 3091, Boca Raton, FL 33431-0991. E-mail: yshibata{at}fau.edu
Different populations of mononuclear phagocytes (MØ) show considerable diversity of cellular function including prostaglandin E2 (PGE2) biosynthesis. Certain bacterial components enhance PGE2 biosynthesis differentially in selected populations of MØ. Interleukin (IL)-10 is proposed to inhibit modulation of PGE2 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 MØ were isolated from IL-10-deficient (IL-10–/–), C57Bl/6 [wild-type (WT) control], and Balb/c (comparison control) mice and were treated with lipopolysaccharide (LPS) and/or interferon-
(IFN-) as a model of bacterial inflammation. LPS-induced PGHS-2 expression was similar for splenic MØ isolated from the three strains of mice. However, PGE2 released by LPS-treated splenic MØ was significantly higher in IL-10–/– and Balb/c than in WT cells. In the presence of LPS and IFN-, PGHS-2 expression and PGE2 release by IL-10–/– and Balb/c splenic MØ were enhanced compared with stimulation with LPS alone or IFN- alone. However, there was no significant increase in PGE2 release from WT splenic MØ treated with LPS plus IFN- despite increased PGHS-2 expression. In sharp contrast, PGHS-2 expression and PGE2 release by bone marrow MØ were greatly enhanced in IL-10–/– cells compared with control cells. Our results indicate that IL-10 regulation of MØ PGE2 biosynthesis and PGHS-2 expression is compartment-dependent and that PGE2 production is not linked directly to PGHS-2 levels. Furthermore, our findings emphasize strain-specific differences between C57Bl/6 and Balb/c mice, and Balb/c appears more similar to the IL-10–/– than to the C57Bl/6 with respect to prostanoid production.
Key Words: PGE2 • PGHS-2 • splenic macrophages • marrow macrophages • LPS
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