Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

Background IL-13 is believed to be a central mediator of asthma, and TGF-β1 is a key downstream mediator in the development of IL-13–mediated asthma phenotypes. Objective To evaluate the biological roles of basic fibroblast growth factor (FGF2) in phenotype expression in transgenic (TG) mice overexp...

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Published in:Journal of allergy and clinical immunology 2007-04, Vol.119 (4), p.831-837
Main Authors: Jeon, Seong Gyu, BSc, Lee, Chun Geun, MD, Oh, Min-Hee, BSc, Chun, Eun-Young, BSc, Gho, Yong Song, PhD, Cho, Sang-Heon, MD, Kim, Jong-Hoon, PhD, Min, Kyung-Up, MD, Kim, You-Young, MD, Kim, Yoon-Keun, MD, Elias, Jack A., MD
Format: Article
Language:English
Subjects:
airway hyperresponsiveness
Allergens - administration & dosage
Allergens - immunology
Allergy and Immunology
Animals
Asthma
Biological and medical sciences
Bronchial Hyperreactivity - pathology
Bronchial Hyperreactivity - physiopathology
Bronchial Hyperreactivity - prevention & control
FGF2
Fibroblast Growth Factor 2 - deficiency
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - therapeutic use
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunopathology
Inflammation Mediators - metabolism
Inflammation Mediators - therapeutic use
Injections, Subcutaneous
Lung - immunology
Lung - metabolism
Lung - pathology
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Migration
Morphogenesis
Mucus - secretion
mucus production
Muscular system
Ovalbumin - administration & dosage
Ovalbumin - immunology
Pathogenesis
Recombinant Proteins - genetics
Recombinant Proteins - therapeutic use
Rodents
Smooth muscle
Transforming Growth Factor beta1 - biosynthesis
Transforming Growth Factor beta1 - metabolism
Wound healing
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Summary:Background IL-13 is believed to be a central mediator of asthma, and TGF-β1 is a key downstream mediator in the development of IL-13–mediated asthma phenotypes. Objective To evaluate the biological roles of basic fibroblast growth factor (FGF2) in phenotype expression in transgenic (TG) mice overexpressing lung-specific TGF-β1, and the therapeutic effects of recombinant FGF2 in the development of asthma phenotypes. Methods To evaluate the roles of FGF2 in airway hyperresponsiveness (AHR) expression induced by high levels of TGF-β1, TGF-β1 TG (+) mice were bred with FGF2-deficient mice. To evaluate the therapeutic effects of recombinant FGF2 (rFGF2) in the development of asthma, mice were given 10 μg of rFGF2 subcutaneously once a day, 1 hour before the allergen challenge in an asthma mouse model. AHR was evaluated using noninvasive whole-body plethysmography, mucus production by diastase-resistant periodic acid Schiff (DPAS) staining, and lung inflammation using bronchoalveolar lavage (BAL) cellularity and lung histology. Results AHR decreased in TGF-β1 TG (+) mice and was accompanied by the upregulation of FGF2 mRNA expression in lung tissues, when compared with littermate wild-type control mice. Interestingly, AHR was enhanced markedly in TGF-β1 (+) mice with homozygous FGF2 gene disruption. In an asthma mouse model, AHR, mucus production, and lung inflammation were inhibited markedly by rFGF2 treatment. This inhibition was accompanied by downregulation of the allergen-induced proliferation of T cells from regional lymph nodes. Conclusion FGF2 seems to be a key inhibitor in the development of AHR, and rFGF2 treatment constrains the development of asthma phenotypes.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2006.12.653