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]
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 Type:||Conference Extract|
|Keywords:||asthma, airway smooth muscle, mouse model|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Zosky, GR (Professor Graeme Zosky)|
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