CIITA expression is regulated by histone deacetylase enzymes and has a role in alpha-synuclein pre-formed fibril-induced antigen presentation in murine microglial cell line

Aim: Parkinson's disease (PD) is a chronic neurodegenerative disorder related with several genetic and epigenetic factors. In the context of epigenetic factors, histone acetylation is one of the most associated mechanisms with Parkinson's disease progression. This study investigates the effects of the increased histone acetylation on antigen presentation in microglial cells which were induced by preformed fibrils of alpha-synuclein (pFF alpha-synuclein). Methods: Parkinson's disease model was created with pFF alpha-synuclein administration to the BV-2 microglial cells. BV-2 cells were co-treated with CUDC-907 and TMP-195 to increase histone acetylation in the presence of alpha-synuclein. Antigen representation was evaluated by determining expression levels of major histocompatibility complex-II (MHC-II) and class-II major histocompatibility complex (CIITA). Results: Our results showed that pFF alpha-synuclein significantly increased MHC-II expression, and that effect was most severe at 6 h of administration of alpha-synuclein. Increasing histone acetylation via CUDC-907 and TMP-195 enhanced MHC-II levels expression, which was more severe in CUDC-907. Additionally, CIITA expression levels were significantly increased with pFF alpha-synuclein administration and intensified with the co-treatment of CUDC-907 and TMP-195. Furthermore, pFF alpha-synuclein caused a time-dependent increase in the IFN-gamma (IFN-gamma) and interleukin-16(IL-16) levels, and that increase was potentiated with CUDC-907 and TMP-195. Conclusion: Changes in MHC-II and CIITA expression indicate that histone acetylation increases the antigen presentation properties of microglial cells after pFF alpha-synuclein or histone deacetylase inhibitor (HDACi) administration. Our results show that microglial antigen presentation might have an essential role in the pathology of Parkinson's disease, and alpha-synuclein likely to play a primary role in this mechanism.