RvE1 and phagocytosis of Porphyromonas gingivalis by PMN in type 2 diabetes (P4227)

Abstract

Abstract Periodontitis is a complication of Type 2 diabetes that impacts control of glycemia and systemic inflammation. Resolution of inflammation is an active, temporally orchestrated process of the biosynthesis of novel mediators (Resolvin E1, RvE1). Dysregulation of resolution may impact human inflammatory diseases such as diabetes and periodontitis. We examined the role of RvE1 in Type 2 diabetes and periodontitis by over-expressing the RvE1 receptor CMKLR1 in Type 2 diabetic mice (db-/-/db-/-); activation pathways and PMN phagocytosis of a periodontal pathogen Porphyromonas gingivalis (P.g.) were compared to wild type (WT), db-/-/db-/- and CMKLR1 over-expressing non-diabetic FVB WT. We report increased progression of periodontitis in diabetic mice is accompanied by impaired PMN phagocytosis. RvE1 enhanced phagocytosis of P.g. by WT PMN, but not PMN from diabetic animals. Phagocytosis was further increased by CMKLR1tg PMN. RvE1 rescued phagocytosis by db-/-/CMKLR1tg PMN. RvE1 induced reductions in AKT and MAPK phosphorylation that were enhanced in the transgenic animals. We conclude that PMN phagocytosis is impaired in db-/-/db-/- mice that is refractory to RvE1. RvE1 enhances PMN phagocytosis in non-diabetic WT mice and rescues impaired PMN phagocytosis in type-2 diabetic mice that over-express CMKLR1. Persistent infection and chronic inflammation characteristic of type 2 diabetes and periodontitis are due, in part, to failure of resolution of inflammation pathways.