Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

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2010-08-24

Autores

de Oliveira, Ana P.L.
Peron, Jean P.S.
Damazo, Amilcar S.
dos Santos Franco, Adriana L.
Domingos, Helori V.
Oliani, Sonia M. [UNESP]
Oliveira-Filho, Ricardo M.
Vargaftig, Bernardo B.
Tavares-de-Lima, Wothan

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Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone.Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin.Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB4 and nitrites while bone marrow cells increased the release of TNF-α and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-α, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF- α by cultured BAL cells and bone marrow cells.Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed. © 2010 de Oliveira et al; licensee BioMed Central Ltd.

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endothelial leukocyte adhesion molecule 1, estradiol, interleukin 10, leukotriene B4, nitrite, ovalbumin, progesterone, tumor necrosis factor alpha, autacoid, sex hormone, allergic pneumonitis, animal cell, animal experiment, animal model, animal tissue, asthma, blood cell, bone marrow cell, cell culture, controlled study, cytokine release, explant, female, human, immunohistochemistry, immunomodulation, in vitro study, leukocyte count, lung lavage, lung parenchyma, nonhuman, oscillation, ovariectomy, ovary, phenotype, postmenopause, protein expression, rat, regulatory mechanism, sensitization, sex hormone determination, animal, biosynthesis, blood, comparative study, immunophenotyping, lung, metabolism, pathology, physiology, respiratory tract allergy, secretion, Wistar rat, Animals, Cells, Cultured, E-Selectin, Estradiol, Female, Gonadal Steroid Hormones, Immunophenotyping, Inflammation Mediators, Lung, Ovariectomy, Progesterone, Rats, Rats, Wistar, Respiratory Hypersensitivity

Como citar

Respiratory Research, v. 11.