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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.

AbstractBACKGROUND:
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.
AuthorsHye Young Yum, Jae Youn Cho, Marina Miller, David H Broide
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 155 Issue 1 Pg. 12-22 ( 2011) ISSN: 1423-0097 [Electronic] Switzerland
PMID21109744 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2010 S. Karger AG, Basel.
Chemical References
  • Adrenal Cortex Hormones
  • Allergens
  • Antigens, Differentiation
  • Transforming Growth Factor beta1
  • monocyte-macrophage differentiation antigen
  • Fibroblast Growth Factor 2
  • Ovalbumin
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
Topics
  • Adrenal Cortex Hormones (pharmacology, therapeutic use)
  • Airway Remodeling (immunology)
  • Allergens (immunology)
  • Animals
  • Antigens, Differentiation (metabolism)
  • Asthma (drug therapy, immunology, metabolism, pathology)
  • Bronchoalveolar Lavage Fluid (chemistry, cytology)
  • Cell Count
  • Disease Models, Animal
  • Eosinophils (pathology)
  • Epithelial Cells (drug effects, metabolism)
  • Female
  • Fibroblast Growth Factor 2 (metabolism, pharmacology)
  • Leukocytes, Mononuclear (immunology, metabolism)
  • Lung (drug effects, metabolism, pathology)
  • Macrophages (drug effects, immunology, metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin (administration & dosage, immunology)
  • Receptor, Fibroblast Growth Factor, Type 1 (metabolism)
  • Transforming Growth Factor beta1 (metabolism)
  • Vaccination

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