title: Protective effects of basic fibroblast growth factor in the development of emphysema induced by interferon-γ.
abstract: Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-γ in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-β, is important in wound healing. We investigated the role of FGF2 in IFN-γ-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-γ-induced emphysema, lung targeted IFN-γ transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic asthma model was generated by airway application of LPS-containing allergens twice a week for 4 weeks. To evaluate protective effects of FGF2, recombinant FGF2 (10 μg) was injected subcutaneously during allergen challenge in the severe asthma model. We found that non-eosinophilic inflammation and emphysema induced by transgenic overexpression of IFN-γ in the airways were aggravated by the absence of FGF2. Airway challenge with LPS-containing allergens induced more inflammation in mice sensitized with LPS-containing allergens compared to challenge with allergens alone. In addition, LPS-induced lung inflammation and emphysema depended on IFN-γ but not on IL-13. Interestingly, emphysema in the severe asthma model was significantly inhibited by treatment with recombinant FGF2 during allergen challenge, whereas lung inflammation was unaffected. Therefore, our present data suggest that FGF2 may help protect against IFN-γ-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.
authors.affiliation: Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung-Jae
authors.initials: BJ
authors.lastname: Lee
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Moon
authors.forename: Tae-Seop
authors.initials: TS
authors.lastname: Shin
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004646:Emphysema / Q000188:drug therapy / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use*; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018793:Interleukin-13; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018793:Interleukin-13; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D007371:Interferon-gamma