Effects of retinoic acid on activation of rat microglia in the primary culture

Abstract

Release of proinflammatory mediators such as tumor necrosis factor-i?! (TNF-i?!) and nitric oxide (NO) by microglia has been implicated in neurotoxicity in chronic neurodegenerative diseases such as Alzheimer's disease. As all-trans retinoic acid (RA) has been reported to exert anti-inflammatory actions in various cell types, we have examined its effects on the expression of TNF-i?! and inducible nitric oxide synthase (iNOS) in microglia induced by I?-amyloid peptide (Ai??) and lipopolysaccharide (LPS). Exposure of primary cultures of rat microglial cells to Ai?? or LPS stimulated the mRNA expression level of TNF-i?! and iNOS significantly. RA acted in a dose-dependent manner (0.1-10i?-M) by attenuating both TNF-i?! and iNOS mRNA expression in microglia exposed to Ai?? or LPS. The anti-inflammatory effects of RA were correlated with the enhancement of the retinoic acid receptor-i?? (RAR-i??), and transforming growth factor-i??1 (TGF-i??1) expression as well as the inhibition of NF-i?<B translocation. These results suggest that RA may inhibit the neurotoxic effect of activated microglia through suppression of cytokine production necessary for microglia activation.