Watanabe Wataru, Hirose Akihiko, Takeshita Tomomi, Hashiguchi Seiko, Sakata Kentaro, Konno Katsuhiko, Miyauchi Aki, Akashi Toshi, Yoshida Hiroki, Sugita Chihiro, Kurokawa Masahiko
Department of Microbiology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare.
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences.
J Toxicol Sci. 2017;42(6):789-795. doi: 10.2131/jts.42.789.
To investigate the effects of perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, on the immune system, a respiratory syncytial virus (RSV) infection mouse model was utilized. Female mice were exposed to TBBPA mixed with the diet from 10 days after conception to weaning on postnatal day 21. Offspring mice were infected intranasally with A2 strain of RSV. Although no general toxicological sign was observed, the pulmonary viral titers of offspring mice exposed to 0.1% TBBPA were significantly increased compared with the control on day 5 post-infection. TBBPA did not affect RSV growth in vitro. Histopathological analysis confirmed that the exacerbation of interstitial pneumonia was due to TBBPA- exposure in the lung tissues in RSV-infected offspring. Moreover, gene expression of interleukin (IL)-24 was shown to be elevated typically in the lung tissues of TBBPA-treated offspring by a DNA microarray and was also confirmed by immunohistopathological analysis using an anti-IL-24 antibody. Thus, developmental exposure to TBBPA affected the immune response to RSV infection, resulting in the exacerbation of pneumonia. Thus, IL-24 should be a key molecule to understand the mechanism of action of TBBPA.
为了研究围产期暴露于溴化阻燃剂四溴双酚A（TBBPA）对免疫系统的影响，使用了呼吸道合胞病毒（RSV）感染小鼠模型。雌性小鼠在受孕后10天至出生后第21天断奶期间，通过饮食接触TBBPA。子代小鼠经鼻内接种RSV A2株。虽然未观察到一般毒理学迹象，但感染后第5天，暴露于0.1% TBBPA的子代小鼠肺病毒滴度与对照组相比显著升高。TBBPA在体外不影响RSV的生长。组织病理学分析证实，间质性肺炎的加重是由于RSV感染子代的肺组织暴露于TBBPA。此外，通过DNA微阵列显示，白细胞介素（IL）-24的基因表达在TBBPA处理的子代肺组织中通常升高，并且使用抗IL-24抗体的免疫组织病理学分析也证实了这一点。因此，发育过程中暴露于TBBPA会影响对RSV感染的免疫反应，导致肺炎加重。因此，IL-24应该是理解TBBPA作用机制的关键分子。
