SIRT2 inhibitors can induce significant increases in the gene expression of pro‐inflammatory factors in primary astrocyte cultures

Abstract

Multiple biological functions of SIRT2 have been reported, including affecting cell mitosis, cell motility, and oligodendrocyte differentiation. SIRT2 inhibitors have also been shown to reduce alpha‐synuclein‐induced neurotoxicity in cellular and Drosophila models of Parkinson's disease. However, there has been no study regarding the role of SIRT2 in neuroinflammation. In this study we determined the effects of SIRT2 inhibition on the gene expression of proinflammatory factors in primary murine astrocyte cultures. We used real‐time PCR assay to show that treatment of astrocytes with 10 micromolar AGK2 ‐‐‐ a selective SIRT2 inhibitor ‐‐‐ for 6 hours induced significant increases in the gene expression of pro‐inflammatory factors: The mRNA levels of TNF‐alpha, iNOS and IL‐6 were increased by 2–11 folds in the AGK2‐treated cells compared with controls. These observations suggest that SIRT2 could be an inhibitory factor of neuroinflammation, and a decrease in SIRT2 levels may lead to neuoinflammation in the brain. Due to the significant roles of neuroinflammation in multiple neurological diseases, our study has suggested that SIRT2 may become a therapeutic target for neurological diseases due to its effects on neuroinflammation (supported by a National Key Basic Research ‘973 Program Grant’ #2010CB834306, a Pujiang Scholar Program Award 09PJ1405900, and a Key Research Grant of Shanghai Municipal Educational Committee #09ZZ21).