Modulation of pulmonary fibrosis by IL-13Rα2

Lumsden, R. V. et al. (2015) Modulation of pulmonary fibrosis by IL-13Rα2. American Journal of Physiology: Lung Cellular and Molecular Physiology, 308(7), L710-L718. (doi: 10.1152/ajplung.00120.2014) (PMID:25659898)

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Abstract

Pulmonary fibrosis is a progressive and fatal disease that involves the remodeling of the distal airspace and the lung parenchyma, which results in compromised gas exchange. The median survival time once diagnosed is less than three years. Interleukin (IL)-13 has been shown to play a role in a number of inflammatory and fibrotic diseases. IL-13 modulates its effector functions via a complex receptor system that includes the IL-4 receptor (R) α, IL-13Rα1, and the IL-13Rα2. IL-13Rα1 binds IL-13 with low affinity, yet, when it forms a complex with IL-4α, it binds with much higher affinity, inducing the effector functions of IL-13. IL-13Rα2 binds IL-13 with high affinity but has a short cytoplasmic tail and has been shown to act as a nonsignaling decoy receptor. Transfection of fibroblasts and epithelial cells with IL-13Rα2 inhibited the IL-13 induction of soluble collagen, TGF-β, and CCL17. Adenoviral overexpression of IL-13Rα2 in the lung reduced bleomycin-induced fibrosis. Our work shows that overexpression of IL-13Rα2 inhibits the IL-13 induction of fibrotic markers in vitro and inhibits bleomycin-induced pulmonary fibrosis. In summary our study highlights the antifibrotic nature of IL-13Ra2.

Item Type:Articles
Additional Information:This work was funded by: Science Foundation Ireland.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Worrell, Dr Julie
Authors: Lumsden, R. V., Worrell, J. C., Boylan, D., Walsh, S. M., Cramton, J., Counihan, I., O'Beirne, S., Medina, M. F., Gauldie, J., Fabre, A., Donnelly, S. C., Kane, R., and Keane, M. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Journal of Physiology: Lung Cellular and Molecular Physiology
Publisher:American Physiological Society
ISSN:1040-0605
ISSN (Online):1522-1504

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