CXCR3 requirement for the interleukin-13–mediated up-regulation of interleukin-13Rα2 in pulmonary fibroblasts

Barnes, J. C. et al. (2015) CXCR3 requirement for the interleukin-13–mediated up-regulation of interleukin-13Rα2 in pulmonary fibroblasts. American Journal of Respiratory Cell and Molecular Biology, 53(2), pp. 217-225. (doi: 10.1165/rcmb.2013-0433OC) (PMID:25514189) (PMCID:PMC5455693)

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Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibrosis and abnormal vascularity. IL-13, a profibrotic cytokine that plays a role in IPF, functions through the Jak/STAT pathway after binding to the IL-13 receptor α1 (IL-13Rα1)/IL-4Rα complex. IL-13 also binds to IL-13Rα2, which has been thought to function as a nonsignaling decoy receptor, although possible signaling roles of this receptor have been proposed. CXCR3 and its IFN-inducible ligands—CXCL9, CXCL10, and CXCL11—have been implicated in vascular remodeling and fibroblast motility during the development of IPF. In this study, CXCR3 expression was demonstrated in cultured pulmonary fibroblasts from wild-type BALB/c mice and was found to be necessary for the IL-13–mediated gene and protein up-regulation of IL-13Rα2. In fibroblasts from CXCR3-deficient mice, STAT6 activation was prolonged. This study is the first to demonstrate the expression of CXCR3 in fibroblasts and its association with the expression of IL-13Rα2. Taken together, the results from this study point strongly to a requirement for CXCR3 for IL-13–mediated IL-13Rα2 gene expression. Understanding the function of CXCR3 in IL-13–mediated lung injury may lead to novel approaches to combat the development of pulmonary fibrosis, whether by limiting the effects of IL-13 or by manipulation of angiostatic pathways. The elucidation of the complex relationship between these antifibrotic receptors and manipulation of the CXCR3-mediated regulation of IL-13Rα2 may represent a novel therapeutic modality in cases of acute lung injury or chronic inflammation that may progress to fibrosis.

Item Type:Articles
Additional Information:This work was supported by Science Foundation Ireland.
Glasgow Author(s) Enlighten ID:Worrell, Dr Julie
Authors: Barnes, J. C., Lumsden, R. V., Worrell, J., Counihan, I. P., O’Beirne, S. L., Belperio, J. A., Fabre, A., Donnelly, S. C., Boylan, D., 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 Respiratory Cell and Molecular Biology
Publisher:American Thoracic Society
ISSN (Online):1535-4989
Published Online:16 December 2015

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