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ABSTRACT: Background
Overexpression of the transforming growth factor ? family signalling molecule smad2 in the airway epithelium provokes enhanced allergen-induced airway remodelling in mice, concomitant with elevated levels of interleukin (IL)-25.Objective
We investigated whether IL-25 plays an active role in driving this airway remodelling.Methods
Anti-IL-25 antibody was given to mice exposed to either inhaled house dust mite (HDM) alone, or in conjunction with an adenoviral smad2 vector which promotes an enhanced remodelling phenotype.Results
Blocking IL-25 in allergen-exposed mice resulted in a moderate reduction in pulmonary eosinophilia and levels of T helper type 2 associated cytokines, IL-5 and IL-13. In addition, IL-25 neutralisation abrogated peribronchial collagen deposition, airway smooth muscle hyperplasia and airway hyperreactivity in control mice exposed to HDM and smad2-overexpressing mice. IL-25 was shown to act directly on human fibroblasts to induce collagen secretion. Recruitment of endothelial progenitor cells to the lung and subsequent neovascularisation was also IL-25 dependent, demonstrating a direct role for IL-25 during angiogenesis in vivo. Moreover, the secretion of innate epithelial derived cytokines IL-33 and thymic stromal lymphopoietin (TSLP) was completely ablated.Conclusions
In addition to modulating acute inflammation, we now demonstrate a role for IL-25 in orchestrating airway remodelling. IL-25 also drives IL-33 and TSLP production in the lung. These data delineate a wider role for IL-25 in mediating structural changes to the lung following allergen exposure and implicate IL-25 as a novel therapeutic target for the treatment of airway remodelling in asthma.
SUBMITTER: Gregory LG
PROVIDER: S-EPMC3534261 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
Gregory Lisa G LG Jones Carla P CP Walker Simone A SA Sawant Devika D Gowers Kate H C KH Campbell Gaynor A GA McKenzie Andrew N J AN Lloyd Clare M CM
Thorax 20121023 1
<h4>Background</h4>Overexpression of the transforming growth factor β family signalling molecule smad2 in the airway epithelium provokes enhanced allergen-induced airway remodelling in mice, concomitant with elevated levels of interleukin (IL)-25.<h4>Objective</h4>We investigated whether IL-25 plays an active role in driving this airway remodelling.<h4>Methods</h4>Anti-IL-25 antibody was given to mice exposed to either inhaled house dust mite (HDM) alone, or in conjunction with an adenoviral sma ...[more]