title: Molecular characterization of antigen-induced lung inflammation in a murine model of asthma.
abstract: Asthma is one of the foremost contributors to morbidity and mortality in industrialized countries. Our objective was to characterize the acute response to allergen and to identify potentially novel molecular targets for pharmacological intervention in asthma. We therefore designed a study to identify genes whose regulation was altered following ovalbumin (OVA) challenge in the presence and absence of treatment with glucocorticoids in BALB/c mice. RNA was isolated from lungs for gene profiling from 8-week-old sensitized mice, 3 and 18 hours post OVA challenge on days 1, 4, and 7 of aerosol challenge. Taqman (real time RT-PCR) analysis of marker genes indicative of Th2 (IL-4, IL-13), eosinophil (RANTES, eotaxin), Th1/macrophage (IFNgamma) and epithelial cell (MUC5AC) phenotypes were used to characterize responses to allergen challenge. Histological evaluation of lungs from additional challenged animals revealed inflammatory infiltrates on days 4 and 7, but not on day 1 post challenge. We postulate that expression of IL-4, IL-13 and other genes by OVA at day 1 probably reflects activation of resident cells, whereas the fivefold increase in the number of regulated genes at day 7 reflects the contribution of recruited cells. Of the regulated genes, only a subset was counter-regulated by dexamethasone treatment. Although regulated genes included genes in many protein families, herein we report regulation of two proteases whose role in response to OVA challenge has not been characterized. This model will be used to generate disease hypotheses for which may play an important role in initiating disease pathology in this model.
authors.affiliation: Department of Respiratory Disease and Rheumatoid Arthritis, Aventis Pharmaceuticals Cambridge, Massachusetts, USA.
authors.forename: Massoud
authors.initials: M
authors.lastname: Daheshia
authors.forename: Nian
authors.initials: N
authors.lastname: Tian
authors.forename: Timothy
authors.initials: T
authors.lastname: Connolly
authors.forename: Amar
authors.initials: A
authors.lastname: Drawid
authors.forename: Quiyan
authors.initials: Q
authors.lastname: Wu
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Bienvenu
authors.forename: Jean
authors.initials: J
authors.lastname: Cavallo
authors.forename: Ray
authors.initials: R
authors.lastname: Jupp
authors.forename: George T
authors.initials: GT
authors.lastname: De Sanctis
authors.forename: Anne
authors.initials: A
authors.lastname: Minnich
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D010047:Ovalbumin