Characteristics of IL-25 and allergen-induced airway fibrosis in a murine model of asthma.
OBJECTIVE
Interleukin (IL)-25 has been implicated in the pathogenesis of human asthma by inducing a Th2 cytokine response, but its possible role in the development of airway remodelling is less clear.


METHODS
We developed a murine surrogate of chronic airway inflammation induced by intranasal application of IL-25 alone. Comparison was with the 'classical' surrogate of ovalbumin (OVA) intranasal instillation into previously sensitized animals. Airway fibrotic biomarkers were analysed by immunohistochemistry and enzyme-linked immunosorbent assay. Additionally, proliferation assay and real-time polymerase chain reaction analysis were performed to assess IL-25's effects on primary human bronchial fibroblasts in vitro.


RESULTS
In Balb/c mice, intranasal instillation of IL-25 alone induced florid airway fibrosis, including increased lay down of extracellular matrix proteins such as collagen I, III, V and fibronectin, increased numbers of fibroblasts/myofibroblasts, a profibrotic imbalance in matrix metalloproteinase/tissue inhibitor of metalloproteinase production and increased expression of profibrotic mediators including connective tissue growth factor and transforming growth factor-β1. These changes broadly reproduced those seen with classical intranasal OVA challenge in OVA-sensitized animals. Furthermore, IL-25 induced proliferation and expression of collagen I and III and smooth muscle α-actin in primary human lung fibroblasts.


CONCLUSIONS
We conclude that chronic exposure of the airways to IL-25 alone is sufficient to cause functionally relevant airway remodelling, with the corollary that targeting of IL-25 may attenuate bronchial remodelling and fibrosis in human asthmatics.
Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China.|Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.|Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University and Beijing Institute of Respiratory Medicine, Beijing, China.
Xiujuan
X
Yao
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Wei
W
Wang
Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University and Beijing Institute of Respiratory Medicine, Beijing, China.
Yan
Y
Li
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Zhe
Z
Lv
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Run
R
Guo
King's College London, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy and Lung Biology, London, UK.
Chris J
CJ
Corrigan
Department of Stomatology, Yidu Central Hospital, Weifang Medical College, Weifang, China.
Gang
G
Ding
Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University and Beijing Institute of Respiratory Medicine, Beijing, China.
Kewu
K
Huang
Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Yongchang
Y
Sun
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.|King's College London, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy and Lung Biology, London, UK.
Sun
S
Ying
D056151:Airway Remodeling / Q000276:immunology; D000485:Allergens / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000008:administration & dosage / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000485:Allergens; D020381:Interleukin-17; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin
IL-25; asthma; fibrosis; murine model; pathogenesis