Yanagisawa Rie, Koike Eiko, Win-Shwe Tin-Tin, Kawaguchi Maiko, Takano Hirohisa
Health and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba, Japan.
Graduate School of Agriculture, Meiji University, Kawasaki, Japan.
Immunopharmacol Immunotoxicol. 2021 Oct;43(5):599-610. doi: 10.1080/08923973.2021.1959609. Epub 2021 Aug 13.
Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphorus flame retardant that is an alternative to brominated flame retardants. Although TDCIPP can adversely affect human health, information about its effects on immune and allergic responses is scarce. We aimed to investigate the effects of dietary exposure to TDCIPP using less than the human tolerable daily intake (TDI) in allergic asthmatic mice.
Male C3H/HeJSlc mice were fed a chow diet containing TDCIPP equivalent to 0.02 μg/kg/day (low; L), 0.2 μg/kg/day (medium; M), or 2 μg/kg/day (high; H) and were intratracheally administered ovalbumin (OVA, 1 μg/animal) every 2 weeks from 5 to 11 weeks of age.
In OVA-treated mice, TDCIPP-H exposure tended to enhance pulmonary inflammation compared with vehicle exposure. TDCIPP dose-dependently decreased mRNA level of G protein-coupled estrogen receptor (GPER) in the lungs with or without OVA. OVA + TDCIPP-H treatment tended to increase the total cell number and promoted CD4 cell activation compared with OVA alone treatment in mediastinal lymph nodes. In splenocytes, an increase in the fraction of Breg cells, but not of total B and T cells, and an increase in IL-5 in cell culture supernatants following OVA re-stimulation in OVA + TDCIPP-H-treated mice was observed compared with OVA-alone-treated mice. Moreover, OVA + TDCIPP-H exposure decreased Gr-1 expression in bone marrow (BM) cells.
These results suggested that dietary exposure to TDCIPP at TDI level slightly enhances allergic diseases, such as allergic asthma, GPER regulation at inflamed sites and secondary lymphoid tissue and BM cell alternations.
磷酸三（1,3 - 二氯 - 2 - 丙基）酯（TDCIPP）是一种有机磷阻燃剂，是溴化阻燃剂的替代品。尽管TDCIPP会对人体健康产生不利影响，但关于其对免疫和过敏反应影响的信息却很少。我们旨在研究在过敏性哮喘小鼠中，低于人类每日可耐受摄入量（TDI）的饮食暴露于TDCIPP的影响。
雄性C3H/HeJSlc小鼠喂食含有相当于0.02μg/kg/天（低剂量；L）、0.2μg/kg/天（中剂量；M）或2μg/kg/天（高剂量；H）的TDCIPP的普通饲料，并在5至11周龄时每2周经气管内给予卵清蛋白（OVA，1μg/只动物）。
在OVA处理的小鼠中，与溶剂暴露相比，TDCIPP - H暴露倾向于增强肺部炎症。无论有无OVA，TDCIPP均剂量依赖性降低肺中G蛋白偶联雌激素受体（GPER）的mRNA水平。与单独OVA处理相比，OVA + TDCIPP - H处理在纵隔淋巴结中倾向于增加总细胞数并促进CD4细胞活化。在脾细胞中，与单独OVA处理的小鼠相比，在OVA + TDCIPP - H处理的小鼠中，OVA再刺激后观察到Breg细胞比例增加，但总B细胞和T细胞比例未增加，并且细胞培养上清液中IL - 5增加。此外，OVA + TDCIPP - H暴露降低了骨髓（BM）细胞中Gr - 1的表达。
这些结果表明，在TDI水平饮食暴露于TDCIPP会轻微增强过敏性疾病，如过敏性哮喘、炎症部位和二级淋巴组织中的GPER调节以及BM细胞改变。
