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

Abstract

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 pre-formed fibrils of α-synuclein (pFF α-synuclein).

Methods

Parkinson’s disease model was created with pFF α-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 α-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 α-synuclein significantly increased MHC-II expression, and that effect was most severe at 6 h of administration of α-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 α-synuclein administration and intensified with the co-treatment of CUDC-907 and TMP-195. Furthermore, pFF α-synuclein caused a time-dependent increase in the IFN-gamma (IFN-ɣ) 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 α-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 α-synuclein likely to play a primary role in this mechanism.

Keywords:

• α-synuclein
• histone deacetylation
• microglia
• antigen presentation

Acknowledgements

We thank Dr. Nihan Cankara and Prof. Arjan Kortholt for invaluable support during experiments.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is derived from the Ph.D. thesis and supported by Ondokuz Mayıs University Research Council [PYO.TIP.1904.19.018].