PGC-1 alpha-Mediated Mitochondrial Biogenesis is Involved in Cannabinoid Receptor 2 Agonist AM1241-Induced Microglial Phenotype Amelioration

摘要

Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1 is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10ng/ml lipopolysaccharide (LPS) plus 10U/ml interferon (IFN) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 mu M AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF-), compared to the cells treated with LPS plus IFN only (P0.05). By using PGC-1-siRNA, however, we found that down-regulation of PGC-1 significantly reversed the AM1241-induced effects above (P0.05). According to the results in this study, we found that PGC-1 may mediate CB2R agonist AM1241-induced anti-inflammation in N9 microglial cells, and the mechanism might be associated with the enhancement of mitochondria biogenesis.