Attenuation of Translocator Protein 18 kDa (TSPO) Up-Regulation by Peroxisome Proliferator-Activated Receptor γ Ligand in Activated Microglia

Abstract

Translocator protein (18 kDa) (TSPO) is a five transmembrane domain protein localized primarily in the outer mitochondrial membrane. Recently, we reported that TSPO is a negative regulator of neuroinflammation in microglia. Peroxisome proliferator-activated receptor (PPAR) is a ligand-specific transcriptional factor belonging to the nuclear receptor superfamily and predicted as a putative TSPO transcriptional factor. A number of studies suggest that the activation of PPARhas anti-inflammatory effects. In this study, we observed that treatment of rosiglitazone, a PPARligand significantly decreased the NO production in lipopolysaccharide-stimulated BV2 microglia cell, indicating inhibition of microglial activation. The inhibitory effect of rosiglitazone extended to attenuated protein level of TSPO. TSPO up-regulation seems an adaptive anti-inflammatory response to overcome microglia activation, according to our previous report. Taken together, these results indicate that PPARactivation by rosiglitazone attenuates neuroinflammation and leads to reduced expression of TSPO in the BV2 microglial cells.