title: Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge.
abstract: BACKGROUND
  IL-13 is believed to be a central mediator of asthma, and TGF-beta1 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-beta1, 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-beta1, TGF-beta1 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 mug 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-beta1 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-beta1 (+) 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.
  
  
  CONCLUSIONS
  FGF2 seems to be a key inhibitor in the development of AHR, and rFGF2 treatment constrains the development of asthma phenotypes.
authors.affiliation: Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Namgu, Pohang, Gyeongbuk, Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Oh
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Chun
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: You-Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000485:Allergens; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D010047:Ovalbumin