title: Modulation of pulmonary fibrosis by IL-13Rα2.
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.
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland;
authors: Robert V
authors: RV
authors: Lumsden
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland;
authors: Julie C
authors: JC
authors: Worrell
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland;
authors: Denise
authors: D
authors: Boylan
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland; Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland;
authors: Sinead M
authors: SM
authors: Walsh
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland;
authors: Jennifer
authors: J
authors: Cramton
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland; Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland;
authors: Ian
authors: I
authors: Counihan
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland; Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland;
authors: Sarah
authors: S
authors: O'Beirne
authors: Fitzhenry Laboratory, Department of Pathology, McMaster University, Hamilton, Ontario, Canada; and.
authors: Maria Fe
authors: MF
authors: Medina
authors: Fitzhenry Laboratory, Department of Pathology, McMaster University, Hamilton, Ontario, Canada; and.
authors: Jack
authors: J
authors: Gauldie
authors: Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland.
authors: Aurelie
authors: A
authors: Fabre
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland; Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland;
authors: Seamas C
authors: SC
authors: Donnelly
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland;
authors: Rosemary
authors: R
authors: Kane
authors: Conway Institute of Biomedical and Biomolecular Science, University College Dublin, Dublin, Ireland; Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland; michael.p.keane@ucd.ie.
authors: Michael P
authors: MP
authors: Keane
mesh_terms: D000818:Animals; D001761:Bleomycin; D054414:Chemokine CCL17 / Q000096:biosynthesis; D003094:Collagen / Q000096:biosynthesis; D057809:HEK293 Cells; D006801:Humans; D018793:Interleukin-13 / Q000502:physiology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D003094:Collagen
keywords: bleomycin; interleukin-13 receptor α2