title: Sex-specific lung remodeling and inflammation changes in experimental allergic asthma.
abstract: There is evidence that sex and sex hormones influence the severity of asthma. Airway and lung parenchyma remodeling and the relationship of ultrastructural changes to airway responsiveness and inflammation in male, female, and oophorectomized mice (OVX) were analyzed in experimental chronic allergic asthma. Seventy-two BALB/c mice were randomly divided into three groups (n=24/each): male, female, and OVX mice, whose ovaries were removed 7 days before the start of sensitization. Each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, the amount of matrix metalloproteinase (MMP)-2 and MMP-9, and the number of eosinophils and interleukin (IL)-4, IL-5, and transforming growth factor (TGF)-β levels in bronchoalveolar lavage fluid were higher in female than male OVA mice. The response of OVX mice was similar to that of males, except that IL-5 remained higher. Nevertheless, after OVA provocation, airway responsiveness to methacholine was higher in males compared with females and OVX mice. In conclusion, sex influenced the remodeling process, but the mechanisms responsible for airway hyperresponsiveness seemed to differ from those related to remodeling.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Antunes
authors.forename: Soraia C
authors.initials: SC
authors.lastname: Abreu
authors.forename: Adriana L
authors.initials: AL
authors.lastname: Silva
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Parra-Cuentas
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Ab'Saber
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Tatiana P T
authors.initials: TP
authors.lastname: Ferreira
authors.forename: Marco A
authors.initials: MA
authors.lastname: Martins
authors.forename: Patricia M R
authors.initials: PM
authors.lastname: Silva
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010052:Ovariectomy; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012737:Sex Factors; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D018836:Inflammation Mediators; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D016210:Methacholine Chloride; D015847:Interleukin-4; D010047:Ovalbumin; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse