Attenuation of Translocator Protein 18 kDa (TSPO) Up-Regulation by Peroxisome Proliferator-Activated Receptor γ Ligand in Activated Microglia
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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 PPARhas anti-inflammatory effects. In this study, we observed that treatment of rosiglitazone, a PPARligand 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 PPARactivation by rosiglitazone attenuates neuroinflammation and leads to reduced expression of TSPO in the BV2 microglial cells.
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 PPARhas anti-inflammatory effects. In this study, we observed that treatment of rosiglitazone, a PPARligand 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 PPARactivation by rosiglitazone attenuates neuroinflammation and leads to reduced expression of TSPO in the BV2 microglial cells.
참고문헌 (17)
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