Type

Journal Article

Authors

Michael P Keane
Rosemary Kane
Denise Boylan
Seamas C Donnelly
Aurélie Fabre
John A Belperio
Sarah L O'Beirne
Ian P Counihan
Julie Worrell
Robert V Lumsden
and 1 others

Subjects

Biochemistry

Topics
ligands acute lung injury fibroblasts il 13 inflammation mice gene expression idiopathic pulmonary fibrosis

CXCR3 is Required for the IL-13 Mediated Upregulation of IL-13Rα2 in Pulmonary Fibroblasts. (2014)

Abstract 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 alpha 1 (IL-13Rα1)/IL-4Rα complex. IL-13 also binds to IL-13Rα2, which has been thought to function as a non-signaling 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 remodelling 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 upregulation 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 both of these anti-fibrotic 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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Michael P Keane, Rosemary Kane, Denise Boylan, Seamas C Donnelly, Aurélie Fabre, John A Belperio, Sarah L O'Beirne, Ian P Counihan, Julie Worrell, Robert V Lumsden and 1 others

Experts in our system

1
Michael P Keane
University College Dublin
Total Publications: 23
 
2
Seamas C Donnelly
TU Dublin (Tallaght Campus)
Total Publications: 35
 
3
Aurélie Fabre
University College Dublin
Total Publications: 15