Oral exposure to low dose bisphenol A aggravates allergic airway inflammation in mice

Rie Yanagisawa; Eiko Koike; Tin-Tin Win-Shwe; Hirohisa Takano

doi:10.1016/j.toxrep.2019.11.012

Oral exposure to low dose bisphenol A aggravates allergic airway inflammation in mice

Toxicol Rep. 2019 Nov 17:6:1253-1262. doi: 10.1016/j.toxrep.2019.11.012. eCollection 2019.

Authors

Rie Yanagisawa¹, Eiko Koike¹, Tin-Tin Win-Shwe¹, Hirohisa Takano²

Affiliations

¹ Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan.
² Graduate School of Global Environmental Studies, Kyoto University, Kyoto, Japan.

Abstract

Bisphenol A (BPA) is widely used in many consumer products and has adverse effects on human health including allergic diseases. We investigated the effects of low dose BPA, comparable to actual human oral exposure, on allergic asthma in mice. C3H/HeJ male mice were fed a chow diet containing BPA (equivalent to 0.09, 0.90, or 9.01 μg/kg/day) and were intratracheally administered ovalbumin (OVA, 1 μg/animal) every two weeks from 5-11 weeks of age. All doses of BPA plus OVA enhanced pulmonary inflammation and airway hyperresponsiveness, and increased lung mRNA levels of Th2 cytokine/chemokine, and serum OVA-specific IgE and IgG₁ compared to OVA alone, with greater effects observed in the middle- and high-dose BPA plus OVA groups. Furthermore, high-dose BPA with OVA decreased lung mRNA levels of ERβ and AR compared with OVA. Furthermore, BPA enhanced OVA-restimulated cell proliferation and protein levels of IL-4 and IL-5 in mediastinal lymph node (MLN) cells in OVA-sensitized mice. In bone marrow (BM) cells, middle-dose BPA with OVA increased Gr-1 expression. In conclusion, oral exposure to low-dose BPA at levels equivalent to human exposure can aggravate allergic asthmatic responses through enhancement of Th2-skewed responses, lung hormone receptor downregulation, and MLN and BM microenvironment change.

Keywords: AhR, aryl hydrocarbon receptor; Allergic asthma; Ar, androgen receptor; BM, bone marrow; BPA, bisphenol a; Bisphenol A; ER, estrogen receptor; Endocrine disruptor; FACS, fluorescence-activated cell-sorting; GR, glucocorticoid receptor; Gr-1, granulocyte-differentiation antigen; Hormone receptor; Hprt1, hypoxanthine phosphoribosyltransferase 1; IFN-γ, interferon-gamma; IL, interleukin; Ig, immunoglobulin; Low dose effects; MCP-1, monocyte chemoattractant protein-1; MIP-1α, macrophage inflammatory protein 1-alpha; MLN, mediastinal lymph node; OVA, ovalbumin; RANTES, normal T cell expressed and secreted; SDF-1α, stromal cell derived factor 1 alpha; Th, T helper; Th2 response.