Expression Pattern and Functions of Dihydropyrimindase Like-3 in the Rodent Microglia

Abstract

This study demonstrates the expression of Dihydropyrimidinase like 3 (Dpysl3), a member of collapsin response mediator protein family, in microglial cells, the resident immune macrophages of the CNS and its role on the inflammatory reaction of microglia. Dpysl3 was intensely expressed in amoeboid microglial cells in the rat brain till postnatal 7th day and then gradually diminished in ramified microglia of adult rats. In vitro analysis confirmed that Dpysl3 expression was induced in activated microglia treated with LPS. It is well documented that LPS induces the expression of iNOS and proinflammatory cytokines in microglia. However, siRNA-mediated knockdown of Dpysl3 prevented the LPS-induced expression of iNOS and cytokines including IL-1?, and TNF-a as well as nuclear translocation of NFkB in microglia. Remarkably, knockdown of Dpysl3 inhibited the migration of activated microglia coupled with deranged actin filament configuration in the cells. Knockdown of Dpysl3 also inhibited the phagocytic capability of activated microglia. These results suggest that knockdown of Dpysl3 can reduce inflammation by inhibiting the activation of microglia.