Effects of Glucocorticoids and retinoic acid on activated rat microglial cells in primary culture

Abstract

An inflammatory process in the central nervous system (CNS) is believed to play an important role in the neuronal cell death in a number of neurodegenerative diseases. The inflammatory response is mediated by the activated microglia, the resident immune cells of the CNS. In response to a variety of stimuli, microglia undergo rapid proliferation, secret a number of proinflammatory cytokines, migrate to the injury sites, and remove the damaged cells by phagocytosis. However, the chronic activation of microglia has been shown to cause neuronal damage through the release of neurotoxic molecules. Therefore, suppression of microglia-mediated inflammation has been considered as an important strategy in neurodegenerative disease therapy. In this study, we analyzed the mechanisms by which Dexamethasone (Dex) and Retinoic Acid (RA) suppress the activation of microglial cells in CNS diseases. Dex inhibits microglial activation and migration by suppressing the release of proinflammatory mediators and chemokines via induction of MKP-1 which negatively regulates MAPKs. RA inhibits the microglial action by suppressing the release of TNF-N1 and NO via MKP-1-mediated inhibition of JNK MAP kinase pathway and the microglial proliferation by regulating cell cycle related protein.