Up-Regulation of FPR2, a Chemotactic Receptor for Amyloid β 1–42 (Aβ42), in Murine Microglial Cells by TNFα

Abstract Human FPRL1 and its mouse homologue FPR2 are functional receptors for several exogenous and host-derived chemotactic peptides, including amyloid β 42 (Aβ 42 ), a critical pathogenic factor in Alzheimer's disease. We investigated the effect of TNFα on the expression and function of FPR2 in mouse microglial cells, a crucial inflammatory cell type in the CNS. Primary murine microglia and a cell line N9 in resting state expressed low levels of FPR2 gene and lacked the response to chemotactic agonists for this receptor. Incubation with TNFα, however, increased microglial expression of FPR2 gene, in association with potent chemotactic responses to FPR2-specific agonists including Aβ 42 . The effect of TNFα was dependent on the p55 TNFα receptor and activation of MAP kinase p38. TNFα concomitantly down-regulated microglial response to the chemokine SDF-1α. Thus, by selectively up-regulating FPR2 in microglia, TNFα has the capacity to amplify host response in inflammatory diseases in the CNS.