Abstract
Abstract Interleukin-27 (p28/EBI3) is expressed by activated antigen presenting cells and has been shown to have immunosuppressive functions including the inhibition of Th17 cell development and the induction of type 1 regulatory T cells (Tr1). In vivo studies demonstrated the anti-inflammatory effects of IL-27 in murine models of collagen-induced arthritis (CIA), inflammatory bowel disease (IBD), and experimental autoimmune encephalomyelitis. We showed previously that PGE2 has proinflammatory effects in models of CIA and IBD through the stimulation of IL-23 production and subsequent development of Th17 cells. Here we report on a novel proinflammatory function through the inhibition of IL-27 production by LPS-stimulated murine BMDC. A similar effect was observed in the dendritic, macrophage and microglia cell lines DC2.4, RAW264.7 and BV2. We determined that the effect of PGE2 was mediated through EP2/EP4 receptors and induction of cAMP. Studies targeting various downstream signaling pathways are in progress. These studies further elucidate the mechanisms involved in the inflammatory role of PGE2, and might identify additional therapeutic targets for the treatment of inflammatory autoimmune diseases.
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