TY - JOUR T1 - Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00068712 SP - erj00687-2012 AU - Rafael Firszt AU - Dave Francisco AU - Tony D. Church AU - Joseph M. Thomas AU - Jennifer L. Ingram AU - Monica Kraft Y1 - 2013/01/01 UR - http://erj.ersjournals.com/content/early/2013/05/16/09031936.00068712.abstract N2 - Airway remodeling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodeling is subepithelial fibrosis. Interleukin-13 (IL-13) is a key TH2 cytokine and is believed to be the central mediator of allergic asthma including remodeling, but the mechanism driving the latter has not been elucidated in human asthma.We hypothesized that IL-13 stimulates collagen type-1 production by the airway fibroblast in a MMP- and TGF-β1-dependent manner in human asthma as compared to healthy controls.Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors.IL-13 significantly stimulated collagen type-1 production in asthma as compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls.In an ex-vivo model, IL-13 potentiates airway remodeling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodeling in asthma. ER -