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

Seong Gyu Jeon, Chun Geun Lee, Min Hee Oh, Eun Young Chun, Yong Song Gho, Sang Heon Cho, Jong-Hoon Kim, Kyung Up Min, You Young Kim, Yoon Keun Kim, Jack A. Elias

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)831-837
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

Fingerprint

Fibroblast Growth Factor 2
Mucus
Allergens
Pneumonia
Asthma
Transgenic Mice
Phenotype
Interleukin-13
Therapeutic Uses
Lung
Whole Body Plethysmography
Periodic Acid
Bronchoalveolar Lavage
Amylases
Histology
Up-Regulation
Down-Regulation
Lymph Nodes
Staining and Labeling
T-Lymphocytes

Keywords

  • airway hyperresponsiveness
  • Asthma
  • FGF2
  • mucus production

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge. / Jeon, Seong Gyu; Lee, Chun Geun; Oh, Min Hee; Chun, Eun Young; Gho, Yong Song; Cho, Sang Heon; Kim, Jong-Hoon; Min, Kyung Up; Kim, You Young; Kim, Yoon Keun; Elias, Jack A.

In: Journal of Allergy and Clinical Immunology, Vol. 119, No. 4, 01.04.2007, p. 831-837.

Research output: Contribution to journalArticle

Jeon, Seong Gyu ; Lee, Chun Geun ; Oh, Min Hee ; Chun, Eun Young ; Gho, Yong Song ; Cho, Sang Heon ; Kim, Jong-Hoon ; Min, Kyung Up ; Kim, You Young ; Kim, Yoon Keun ; Elias, Jack A. / Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 119, No. 4. pp. 831-837.
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T1 - Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

AU - Jeon, Seong Gyu

AU - Lee, Chun Geun

AU - Oh, Min Hee

AU - Chun, Eun Young

AU - Gho, Yong Song

AU - Cho, Sang Heon

AU - Kim, Jong-Hoon

AU - Min, Kyung Up

AU - Kim, You Young

AU - Kim, Yoon Keun

AU - Elias, Jack A.

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Y1 - 2007/4/1

N2 - 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.

AB - 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.

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