Exp Mol Med.  2011 Apr;43(4):169-178. 10.3858/emm.2011.43.4.018.

Protective effects of basic fibroblast growth factor in the development of emphysema induced by interferon-gamma

• Lee BJ
• Moon HG
• Shin TS
• Jeon SG
• Lee EY
• Gho YS
• Lee CG
• Zhu Z
• Elias JA
• Kim YK

• KMID: 1104386
• DOI: http://doi.org/10.3858/emm.2011.43.4.018

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-gamma in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-beta, is important in wound healing. We investigated the role of FGF2 in IFN-gamma-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-gamma-induced emphysema, lung targeted IFN-gamma 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 microg) 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-gamma 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-gamma 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-gamma-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.

Keyword

asthma; emphysema; fibroblast growth factor 2; interferon-gamma; pulmonary eosinophilia

MeSH Terms

Animals
Asthma/drug therapy/*prevention & control
Bronchoalveolar Lavage Fluid
Disease Models, Animal
Emphysema/drug therapy/*prevention & control
Enzyme-Linked Immunosorbent Assay
Fibroblast Growth Factor 2/deficiency/*metabolism/*therapeutic use
Flow Cytometry
Inflammation/immunology
Interferon-gamma/*biosynthesis/genetics
Interleukin-13
Lipopolysaccharides/administration & dosage/pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Pulmonary Eosinophilia
Recombinant Proteins/administration & dosage/therapeutic use