Prolonged allergen challenge in mice leads to persistent airway remodelling
- 9 March 2004
- journal article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 34 (3), 497-507
- https://doi.org/10.1111/j.1365-2222.2004.01895.x
Abstract
Background Inflammatory infiltrates, airway hyper‐responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen‐induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. Objective The aim of this study was to use a murine model of prolonged allergen‐induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge. Methods Acute pulmonary eosinophilia and airways hyper‐reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80). Results The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up‐regulation of IL‐4 and tumour growth factor‐β1 during the chronic phase. Interestingly, while IL‐4 levels were significantly increased during the chronic phase, levels of IL‐13 fell. Levels of the Th1‐associated cytokine IFN‐γ also increased during the chronic phase. Conclusion In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.Keywords
This publication has 54 references indexed in Scilit:
- Interleukin-5 Expression in the Lung Epithelium of Transgenic Mice Leads to Pulmonary Changes Pathognomonic of AsthmaThe Journal of Experimental Medicine, 1997
- Altered compartimentalization of transforming growth factor-β in asthmatic airwaysClinical and Experimental Allergy, 1997
- Altered compartimentalization of transforming growth factor-beta in asthmatic airwaysClinical and Experimental Allergy, 1997
- Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.JCI Insight, 1996
- Interleukin-4 and interferon-γ discordantly regulate collagen biosynthesis by functionally distinct lung fibroblast subsetsJournal of Cellular Physiology, 1996
- Interleukin‐4 and interferon‐γ discordantly regulate collagen biosynthesis by functionally distinct lung fibroblast subsetsJournal of Cellular Physiology, 1996
- Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.The Journal of Experimental Medicine, 1996
- The Role of Mucus in Chronic Obstructive Pulmonary DiseaseChest, 1990
- Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytesNature, 1980
- A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysemaThorax, 1969