Airway remodelling is a feature of
asthma that contributes to loss of lung function. One of the central components of
airway remodelling is subepithelial
fibrosis.
Interleukin (IL)-13 is a key T-helper 2
cytokine and is believed to be the central mediator of allergic
asthma including remodelling, but the mechanism driving the latter has not been elucidated in human
asthma. We hypothesised that
IL-13 stimulates
collagen type-1 production by the airway fibroblast in a
matrix metalloproteinase (
MMP)- and
transforming growth factor (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 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 remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed
airway remodelling in
asthma.