Microarray Analysis of the Effects of Amelogenin on U937 Monocytic Cells

Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly by monocytes and macrophages in this immune response, and will be presented to lymphocytes. Recently, therapies for regenerating periodontal tissues have been used extensively to treat periodontal disease, and in particular, enamel matrix derivative (EMD) is commonly used for such therapies in Japan. Amelogenin is a type of the extracellular matrix protein that accounts for 90% of the constituents of EMD. In this study, we carried out a detailed microarray analysis in order to evaluate a gene group involved in amelogenin stimuli in the human monocytic cell line U-937. Microarray analysis revealed that statistically significant changes were apparent in 273 genes (163 up-regulated and 110 down-regulated) subsequent to 4 h of amelogenin stimulation. The most highly enriched categories included “cell cycle”, “DNA replication”, and “DNA repair” in up-regulated annotation terms. On the other hand, “type I diabetes mellitus”, “allograft rejection”, and “graft versus host disease” were observed in down-regulated annotation terms. Specifically, the gene expression of major to compatibility complex (MHC) class I/II and CD80/86 was impaired in U937 cells after stimulation with amelogenin. In addition, the results of heat-map showed that the gene expression of inflammatory cytokine such as tumor necrosis factor (TFN), interleukin-18 (IL-18), and CXCL16 was markedly decreased after stimulation of monocytes with amelogenin. In conclusion, the findings of our study showed that by inducing monocyte growth through the suppression of the antigen-presenting ability of U937 cells, amelogenin may affect the immune responses of periodontal tissues originating from monocytes. Examining the effects of amelogenin on the transformation of macrophages differentiating from monocytes may establish a molecular baHow to cite this paper: Sanui, T., Fukuda, T., Yamamichi, K., Toyoda, K., Tanaka, U., Yotsumoto, K., Taketomi, T. and Nishimura, F. (2017) Microarray Analysis of the Effects of Amelogenin on U937 Monocytic Cells. American Journal of Molecular Biology, 7, 107-122. https://doi.org/10.4236/ajmb.2017.72009 Received: February 23, 2017 Accepted: April 27, 2017 Published: April 30, 2017 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access