Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gungl, A; Biasin, V; Wilhelm, J; Olschewski, A; Kwapiszewska, G; Marsh, LM.
Fra2 Overexpression in Mice Leads to Non-allergic Asthma Development in an IL-13 Dependent Manner.
Front Immunol. 2018; 9(10):2018-2018
Doi: 10.3389/fimmu.2018.02018
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- Führende Autor*innen der Med Uni Graz
- Birnhuber Anna
- Marsh Leigh
- Co-Autor*innen der Med Uni Graz
- Biasin Valentina
- Kwapiszewska-Marsh Grazyna
- Olschewski Andrea
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- Abstract:
- Background: Asthma is a complex chronic inflammatory disease characterised by airway inflammation, remodelling and hyperresponsiveness (AHR). Members of the AP-1 transcription factor family play important roles in the activation of the immune system and the control of cellular responses; however, their role in the development of asthma has not been well studied. We aimed to investigate the role of the lesser known AP-1 family member, Fra2 in experimental asthma. Methods: Phenotypic characterisation and gene expression profiling was performed on Fra2 (TG) overexpressing and wild-type mice. The efficacy of therapeutic interventions in regulating the Fra2 phenotype was determined. Results: Transcriptional profiling of TG mice revealed a high abundance of regulated genes associated with airway remodelling, inflammation and mucus production. A concomitant increase in peribronchial collagen deposition, smooth muscle thickening and mucus production was observed. TG mice possessed increased inflammatory infiltration in the lung, predominantly consisting of eosinophils and T-cells and elevated expression of Th2 cytokines and eotaxin. Furthermore, TG mice possessed severe AHR in response to increasing doses of methacholine. Glucocorticoid treatment led to a partial improvement of the asthma phenotype, whereas blockade of IL-13 via neutralising antibodies ameliorated AHR and mucus production, but had no effect on collagen deposition. Conclusion: We here describe a novel model for non-allergic asthma that does not require the application of exogenous allergens, which mimics several key features of the disease, such as airway inflammation, remodelling and hyperresponsiveness. Fra2 may represent a key molecule coordinating multiple aspects of asthma pathogenesis.
- Find related publications in this database (Keywords)
- extrinsic asthma
- AP-1
- airway hyperresponsiveness
- Fra-2
- mucus hypersecretion