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

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, e...

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Autores principales: Loffredo, Lucas Fedele, Coden, Mackenzie Elyse, Berdnikovs, Sergejs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071314/
https://www.ncbi.nlm.nih.gov/pubmed/32012983
http://dx.doi.org/10.3390/nu12020343
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author Loffredo, Lucas Fedele
Coden, Mackenzie Elyse
Berdnikovs, Sergejs
author_facet Loffredo, Lucas Fedele
Coden, Mackenzie Elyse
Berdnikovs, Sergejs
author_sort Loffredo, Lucas Fedele
collection PubMed
description 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.
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spelling pubmed-70713142020-03-19 Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice Loffredo, Lucas Fedele Coden, Mackenzie Elyse Berdnikovs, Sergejs Nutrients Article 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. MDPI 2020-01-28 /pmc/articles/PMC7071314/ /pubmed/32012983 http://dx.doi.org/10.3390/nu12020343 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Loffredo, Lucas Fedele
Coden, Mackenzie Elyse
Berdnikovs, Sergejs
Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title_full Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title_fullStr Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title_full_unstemmed Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title_short Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice
title_sort endocrine disruptor bisphenol a (bpa) triggers systemic para-inflammation and is sufficient to induce airway allergic sensitization in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071314/
https://www.ncbi.nlm.nih.gov/pubmed/32012983
http://dx.doi.org/10.3390/nu12020343
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