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Independent effects of airway smooth muscle remodelling and allergic inflammation on airway responsiveness

Citation

Wang, K and Le Cras, T and Larcombe, A and Zosky, GR and James, A and Noble, P, Independent effects of airway smooth muscle remodelling and allergic inflammation on airway responsiveness, Respirology, 27 March - 1 April, 2015, Gold Coast, Australia, pp. 23. ISSN 1323-7799 (2015) [Conference Extract]


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DOI: doi:10.1111/resp.12494

Abstract

Aim: Inflammatory and structural abnormalities of the airways are features of asthma, however their interrelationship is unclear. This study determined the separate and combined effects of increased thickness of the airway smooth muscle (ASM) layer and allergic inflammation on airway responsiveness. Methods: We integrated a protocol of induced allergic airway inflammation in a non-inflammatory mouse model of ASM remodelling. The latter was achieved by conditional expression of TGFα in the airway epithelium of Egr-1 deficient transgenic mice (Clara cell secretory protein-rtTA(+/−)/[tetO](7)-TGFα(+/−)) which produces thickening of the ASM layer following exposure to doxycycline in chow. Mice were sensitised to ovalbumin and assigned to one of four groups: a single ovalbumin challenge (OVA, n = 5); 10d doxycycline and saline challenge (Dox, n = 7); combined doxycycline and OVA treatments (Dox/OVA, n = 7); saline challenge alone (Control, n = 6). Twenty four hours after challenge, airway responsiveness to methacholine was assessed by the forced oscillation technique.

Results: Compared with the control group, airway responsiveness to methacholine was increased in the OVA (P = 0.006), Dox (P = 0.035) and Dox/OVA groups (P = 0.005) but airway responsiveness in the Dox/OVA group was not different from either the Dox (P = 0.284) or OVA (P = 0.154) groups. There was no difference in baseline airway resistance between groups.

Conclusion: Allergic inflammation does not enhance airway hyperresponsiveness produced by thickening of the ASM layer. These findings do not support a necessary causal relationship between allergic airway inflammation and remodelling which may instead be independent causes of variable and excessive airway narrowing.

Item Details

Item Type:Conference Extract
Keywords:asthma, airway smooth muscle, mouse model
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Zosky, GR (Associate Professor Graeme Zosky)
ID Code:102381
Year Published:2015
Deposited By:Medicine (Discipline)
Deposited On:2015-08-17
Last Modified:2015-08-19
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