Allergen-Induced Coexpression of bFGF and TGF-?1 by Macrophages in a Mouse Model of Airway Remodeling: bFGF Induces Macrophage TGF-?1 Expression in vitro.
Int Arch Allergy Immunol. 2010 Nov 25;155(1):12-22
Authors: Yum HY, Cho JY, Miller M, Broide DH
Background: Basic fibroblast growth factor (bFGF) is a cytokine that is mitogenic for fibroblasts and smooth muscle and may play a role in airway remodeling in asthma. We have used a mouse model of chronic ovalbumin (OVA) allergen-induced airway remodeling to determine whether bFGF and fibroblast growth factor receptor-1 are expressed and regulated by corticosteroids in the airway, as well as to determine whether bFGF mediates expression of another proremodeling cytokine, transforming growth factor (TGF)-?1. Methods: The airway levels and localization of bFGF, FGF receptor-1 and TGF-?1 were determined by ELISA, immunohistology and image analysis in the remodeled airways of chronic OVA-challenged mice treated with either corticosteroids or diluent. In vitro cultures of bone narrow-derived macrophages were used to determine whether bFGF induced TGF-?1 expression. Results: Mice chronically challenged with OVA developed significant airway remodeling that was associated with significantly increased levels of bFGF and TGF-?1. Immunohistochemistry demonstrated significantly increased bFGF and FGF receptor-1 expression by peri- bronchial F4/80+ cells. Double-label immunofluorescence microscopy studies demonstrated that peribronchial macrophages coexpressed bFGF and TGF-?1. In vitro studies demonstrated that incubation of bone marrow-derived macrophages with bFGF induced expression of TGF-?1. Mice treated with corticosteroids and subjected to chronic OVA challenge had significantly reduced levels of bFGF, FGF receptor-1, peribronchial TGF-?1+ cells and airway remodeling. Conclusions: Overall, this study demonstrates that allergen challenge stimulates peribronchial macrophages to coexpress bFGF and TGF-?1 and that bFGF may potentiate macrophage release of TGF-?1 through autocrine and/or paracrine pathways.
PMID: 21109744 [PubMed – as supplied by publisher]
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