Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice

Abstract

Allergic airway diseases are accompanied by increased permeability and an inflammatory state of epithelial barriers, which are thought to be susceptible to allergen sensitization. Although exogenous drivers (proteases, allergens) of epithelial barrier disruption and sensitization are well studied, endogenous contributors (diet, xenobiotics, hormones, and metabolism) to allergic sensitization are much less understood. Xenoestrogens are synthetic or natural chemical compounds that have the ability to mimic estrogen and are ubiquitous in the food and water supply of developed countries. By interfering with the estrogen produced by the endocrine system, these compounds have the systemic potential to disrupt the homeostasis of multiple tissues. Our study examined the potential of prototypical xenoestrogen bisphenol A (BPA) to disrupt epithelial homeostasis in vitro and promote allergic responses in vivo. We found that BPA exposure in epithelial cultures in vitro significantly inhibited epithelial cell proliferation and wound healing, as well as promoted the expression of the innate alarmin cytokine TSLP in a time-and dose-dependent manner. In vivo, the exposure to BPA through water supply or inhalation induced a systemic para-inflammatory response by promoting the expression of innate inflammatory mediators in the skin, gut, and airway. In a murine tolerogenic antigen challenge model, chronic systemic exposure to BPA was sufficient to induce airway sensitization to innocuous chicken egg ovalbumin in the complete absence of adjuvants. Mechanistic studies are needed to test conclusively whether endocrine disruptors may play an upstream role in allergic sensitization via their ability to promote a para-inflammatory state.

The influence of bisphenol A on the human body

“…Additionally, this substance promoted the expression of the cytokine TSLP. In vivo, BPA significantly induced systemic inflammation as the levels of inflammatory mediators in the skin, intestines and respiratory system increased [32]. A similar study was conducted in which an exacerbation of allergy to egg proteins was observed as a result of exposure to BPA.…”

Endocrine-disrupting chemicals and their effects on puberty

“…Thus they alter gene expression as well as intracellular transduction pathways [79]. After incorporation they can also compete with endogenous hormones and other substances for binding to carrier proteins [80] or metabolization and interfere with epithelial cells triggering systemic para-inflammation [81].…”

Targeting p-AKT/mTOR/MAP kinase signaling, NLRP3 inflammasome and apoptosis by fluvastatin with or without taxifolin mitigates gonadal dysfunction induced by bisphenol-A in male rats

“…2 Recent reports paid the attention towards the findings that chronic exposure to BPA may cause endocrinal dysfunction. 3,4 These findings might be attributed to the close similarity between the phenol groups in both BPA and estradiol, which may confer an effect to BPA on the estrogenic pathways in the body. 5 In addition, high concentrations of BPA were proven to block the androgen receptors (AR), modulate Leydig cell steroidogenesis, and hinder LH receptor-ligand binding.…”