Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.

Firszt, Rafael

Francisco, Dave

Church, Tony D

Thomas, Joseph M

Ingram, Jennifer L

Kraft, Monica

2022-07-01T15:03:41Z

2022-07-01T15:03:41Z

2014-02

2022-07-01T15:03:40Z

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.

09031936.00068712

0903-1936

1399-3003

https://hdl.handle.net/10161/25436

eng

European Respiratory Society (ERS)

The European respiratory journal

10.1183/09031936.00068712

Bronchi

Fibroblasts

Humans

Asthma

Collagen Type I

Actins

Transforming Growth Factor beta

Extracellular Matrix Proteins

Interleukin-13

Respiratory Function Tests

Biopsy

Gene Expression Regulation

Adult

Female

Male

Matrix Metalloproteinase 2

Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.

Journal article

Ingram, Jennifer L|0000-0002-5269-8864

464

473

2

Duke

School of Medicine

Faculty

Clinical Science Departments

Medicine

Pathology

Surgery

Medicine, Pulmonary, Allergy, and Critical Care Medicine

Surgery, Surgical Sciences

Published

43