CD200 selectively upregulates prostaglandin E2 and D2 synthesis in LPS-treated bone marrow-derived macrophages

Abstract

The CD200/CD200R signalling pathway downregulates the synthesis of proinflammatory mediators and induces the synthesis of antiinflammatory mediators in macrophages and microglia. However, very little is known about the effect of this immunosuppressive pathway on the synthesis of lipid mediators. Therefore, we determined the synthesis of 35 lipids spanning 5 different lipid families in bone marrow-derived macrophages, which were treated with interleukin (IL) 4, IL10, lipopolysaccharide (LPS), or interferon γ (IFNγ) in absence and presence of CD200. Out of these conditions the only significant effect of CD200 was an increased synthesis of prostaglandin (PG) E₂ and D₂ in the presence of LPS. Accordingly, mRNA levels of cyclooxygenase-2, microsomal PGE₂ synthase-1 and hematopoietic PGD synthase were upregulated by CD200 in presence of LPS. During Complete Freund's Adjuvant (CFA-) induced inflammation mPGES-1 was expressed in monocyte-derived macrophages and its expression was stronger in CD200R-positive than in CD200R-negative macrophages.

Keywords: CD200; COX-2; HPGDS; Macrophages; Prostaglandin; mPGES-1.