Health and Environmental Risk Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
Graduate School of Global Environmental Studies, Kyoto University, Kyoto Daigaku-Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
Int J Mol Sci. 2022 Sep 15;23(18):10790. doi: 10.3390/ijms231810790.
Bisphenol S (BPS) is increasingly being used as an alternative for bisphenol A; however, its health effects remain unclear. We investigated the effects of oral exposure to low-dose BPS on allergic asthma. C3H/HeJ male mice were intratracheally administered with allergen (ovalbumin (OVA), 1 μg/animal) every 2 weeks from 6 to 11 weeks old. BPS was ingested by drinking water at doses equivalent to 0.04, 0.4, and 4 μg/kg/day. We then examined pulmonary inflammation, airway hyperresponsiveness, serum OVA-specific immunoglobulin (Ig) levels, Th2 cytokine/chemokine production, and mediastinal lymph node (MLN) cell activities. Compared with OVA alone, moderate-dose BPS (BPS-M) with OVA significantly enhanced pulmonary inflammation, airway hyperresponsiveness, and OVA-specific IgE and IgG1. Furthermore, interleukin (IL)-5, IL-13, IL-33, and CCL11/Eotaxin protein levels in the lungs increased. Conversely, these allergic responses were reduced in the high-dose BPS+OVA group. In MLN cells, BPS-M with OVA increased the total cell count and activated antigen-presenting cells including conventional dendritic cell subset (cDC2). After OVA restimulation, cell proliferation and Th2 cytokine production (IL-4, IL-5, and IL-13) in the culture supernatant also increased. Therefore, oral exposure to low-dose BPS may exacerbate allergic asthmatic responses by enhancing Th2-polarized responses and activating the MLN cells.
双酚 S(BPS)作为双酚 A 的替代品,其应用日益广泛,但它对健康的影响尚不清楚。我们研究了经口摄入低剂量 BPS 对变应性哮喘的影响。C3H/HeJ 雄性小鼠在 6 至 11 周龄时,每 2 周经气管内给予过敏原(卵清蛋白(OVA),1 μg/动物)。BPS 通过饮用水摄入,剂量分别相当于 0.04、0.4 和 4 μg/kg/天。然后,我们检查了肺部炎症、气道高反应性、血清 OVA 特异性免疫球蛋白(Ig)水平、Th2 细胞因子/趋化因子产生以及纵隔淋巴结(MLN)细胞活性。与 OVA 单独相比,中剂量 BPS(BPS-M)与 OVA 显著增强了肺部炎症、气道高反应性和 OVA 特异性 IgE 和 IgG1。此外,肺组织中白细胞介素(IL)-5、IL-13、IL-33 和 CCL11/Eotaxin 蛋白水平增加。相反,高剂量 BPS+OVA 组的这些过敏反应减少。在 MLN 细胞中,BPS-M 与 OVA 增加了总细胞计数和激活的抗原呈递细胞,包括常规树突状细胞亚群(cDC2)。OVA 再刺激后,培养上清液中的细胞增殖和 Th2 细胞因子(IL-4、IL-5 和 IL-13)的产生也增加。因此,经口摄入低剂量 BPS 可能通过增强 Th2 极化反应和激活 MLN 细胞,加重变应性哮喘反应。