Allergen-induced coexpression of bFGF and TGF-β1 by macrophages in a mouse model of airway remodeling: bFGF induces macrophage TGF-β1 expression in vitro.
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)-β1.


METHODS
The airway levels and localization of bFGF, FGF receptor-1 and TGF-β1 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-β1 expression.


RESULTS
Mice chronically challenged with OVA developed significant airway remodeling that was associated with significantly increased levels of bFGF and TGF-β1. 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-β1. In vitro studies demonstrated that incubation of bone marrow-derived macrophages with bFGF induced expression of TGF-β1. Mice treated with corticosteroids and subjected to chronic OVA challenge had significantly reduced levels of bFGF, FGF receptor-1, peribronchial TGF-β1+ cells and airway remodeling.


CONCLUSIONS
Overall, this study demonstrates that allergen challenge stimulates peribronchial macrophages to coexpress bFGF and TGF-β1 and that bFGF may potentiate macrophage release of TGF-β1 through autocrine and/or paracrine pathways.
Department of Medicine, University of California San Diego, USA.
Hye Young
HY
Yum
Jae Youn
JY
Cho
Marina
M
Miller
David H
DH
Broide
D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D056151:Airway Remodeling / Q000276:immunology*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014611:Vaccination
D000305:Adrenal Cortex Hormones; D000485:Allergens; D000943:Antigens, Differentiation; D053773:Transforming Growth Factor beta1; C036763:monocyte-macrophage differentiation antigen; D016222:Fibroblast Growth Factor 2; D010047:Ovalbumin; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1