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      The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin

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          Abstract

          OBJECTIVE:

          Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation.

          METHOD:

          Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later.

          RESULTS:

          Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation.

          CONCLUSION:

          In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammation.

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          Most cited references47

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          Modulating leukocyte recruitment in inflammation.

          Much information has been obtained regarding how white cells are recruited in the microcirculation to sites of inflammation. In this review we summarize the leukocyte recruitment cascade, highlighting the molecular mechanisms that underlie each of the major steps. Major emphasis is placed on the selectins and integrins and their role in rolling and adhesion. Intraluminal crawling and emigration are also briefly discussed. In addition, we summarize some of the data that implicate these molecules in eosinophil recruitment in animal models of asthma and in lymphocyte recruitment in skin contact sensitivity. There is a growing body of evidence to suggest that leukocyte recruitment could be used as an effective means for future therapeutics, and some of these issues are also raised.
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            The impact of estrogen and progesterone on asthma.

            This paper describes evidence of a positive effect of both endogenous and exogenous estrogen and progesterone on lung function across the life span in women. Articles were identified using the keywords asthma, pulmonary function, menarche, menopause, estrogen, progesterone, hormone replacement therapy, oral contraceptives, and menstrual cycle from years 1966 to 2001 in MEDLINE. Additional studies were identified from article reference lists. Relevant, peer-reviewed original research articles in the English language were selected. Estrogen and/or progesterone may alter pulmonary function and asthma. Premenopausal women experience decreases in pulmonary function and increases in asthma exacerbations and hospitalizations during the premenstrual and menstrual phases. Oral contraceptives and hormone replacement therapy are associated with improved pulmonary function and decrease in asthma exacerbation. Some asthmatic patients experience improved pulmonary function and reduced asthma medication requirement during pregnancy. Estrogen and progesterone modify airway responsiveness. Further research is needed to elucidate the clinical relevance of estrogen and progesterone in the pathophysiology and therapy of asthma.
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              Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma.

              Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone. This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase. Progesterone worsened allergic airway inflammation in OVA-challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL-5 levels in the progesterone group. The ratio of IL-4/IFN-gamma levels in bronchoalveolar lavage fluid and numbers of eosinophil colony-forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen-specific IgE production, nor did it affect bronchial responses in Sal-challenged mice. Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL-5 production. Progesterone also increases bronchial hyper-reactivity.
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                Author and article information

                Journal
                Clinics (Sao Paulo)
                Clinics (Sao Paulo)
                Clinics
                Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
                1807-5932
                1980-5322
                December 2013
                : 68
                : 12
                : 1528-1536
                Affiliations
                [I ]Universidade de São Paulo, Institute of Biomedical Sciences, Department of Pharmacology, São Paulo/SP, Brazil.
                [II ]Universidade de São Paulo, Faculty of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, São Paulo/SP, Brazil.
                [III ]Nove de Julho University, Department of Biophotonics, São Paulo/SP, Brazil.
                [IV ]Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil.
                [V ]Universidade de Cuiabá (UNIC), Faculty of Medical Sciences, Department of Basic Science in Health, Cuiaba/MT, Brazil.
                Author notes

                Lino-dos-Santos-Franco A performed the airway reactivity study and wrote the manuscript. Amemiya RM and Vitoretti L performed the OVx and cellular analyses. Acceturi BG performed the OVx. Oliveira AP quantified the IL-10 cytokine results. Breithaupt-Faloppa AC evaluated the MPO activity and helped write the manuscript. Damazo AS performed the mast cell analysis. Lima WT revised the manuscript.

                E-mail: adrilino@ 123456usp.br Tel.: 55 11 3091-2197
                Article
                cln_68p1528
                10.6061/clinics/2013(12)09
                3840370
                2be8c0ea-92f2-4961-9232-d348fc215548
                Copyright © 2013 Hospital das Clínicas da FMUSP

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2013
                : 30 May 2013
                : 5 June 2013
                Page count
                Pages: 9
                Categories
                Basic Research

                Medicine
                formaldehyde exposure,lung inflammation,progesterone,tracheal reactivity,mast cells,interleukin-10

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