Effects of organic compounds adsorbed on air pollution particulate matter on estrogen receptors, aryl-hydrocarbon and P-450 in the airway epithelium in male and female mice

Abstract

The exposure to particles and gases from air pollution has a great impact on the health of humans and animals. One hypothesis is related to chemicals released by air pollution particles, mainly the organic compounds adsorbed to them, which act as an endocrine releaser. These interfere with the normal functioning of the endocrine system by mimicking or antagonizing hormones that occurs with the hormones and/or the modulation of hormonal responses, which may lead to adverse health effects such as the release of gonadal steroids. The aim of this study is to: i) identify and quantify the female hormone receptor in the airway mucosa of mice, ii) verify if air pollution affects the expression of the receptors for the estrogen hormones and their competitor, AhR, observing whether these changes occur in the epithelium of males and iii) verify if these changes in the Ahr receptor directly interferes with the adhesion molecules E-cadherin, alpha-catenin and E-cytokines IL-8, TNF, IL-17, IL-1², TGF-±, prostaglandins COX-2 and MMP, insofar as they bear a direct relationship with asthma and allergic diseases and COPD. Methodology: 14 male and 56 female BALB/c mice, young adults with 20 days of age, will be exposed to 600 mg/m3 (the concentration received per day - 24 hours - in the city of São Paulo) using an ambient particle concentrator (APC) for a period of at least 45 days. They will be sacrificed at 3 menstrual cycles: 14 female in estrus (E), 14 in diestrus (D) 14 in pro-oestrus (PE), besides 14 males (M). We will study the presence of estrogen and progesterone receptors, as well as the dioxin/aryl hydrocarbon (AhR) receptor (-an important competitor of estrogenic receptors in the transcriptional regulation of genes coding for xenobiotic metabolizing enzymes such as cytochrome P450 enzymes) and the P450 family enzymes (CYP1A1, CYP1A2 and CYP1B1). To that end, we will use immunohistochemistry to study the presence of progesterone and estrogen receptors alpha (ER-alpha) and estrogen (ER-beta), dioxin receptor/aryl hydrocarbon (AhR) and CYP1A1 and CYP1A2 and CYP1B1. Additionally, we will verify ER-alfa, ER-beta AhR P-450 gene expression levels when subjected to the APC through PCR-RT. These will be correlated with IL-8, TNF, IL-17, IL-1², TGF-± and MMP cytosines, COX-2 prostaglandins, and E-cadherin, alpha-catenin-E adhesion molecules. (AU)