Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.
Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.
Department of Allergy and Immune Disorders, Murdoch Children's Research Institute Melbourne, Victoria, Australia.
Simon G
SG
Royce
Clarice
C
Lim
Ruth C
RC
Muljadi
Chrishan S
CS
Samuel
Katherine
K
Ververis
Tom C
TC
Karagiannis
Andrew S
AS
Giraud
Mimi L K
ML
Tang
D000199:Actins / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000494:pharmacology / Q000502:physiology*; D009124:Muscle Proteins / Q000494:pharmacology / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000071164:Trefoil Factor-2
D000199:Actins; D017304:Annexin A5; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D011994:Recombinant Proteins; C481546:TFF2 protein, mouse; D053773:Transforming Growth Factor beta1; D000071164:Trefoil Factor-2; C544013:alpha-smooth muscle actin, mouse; D010047:Ovalbumin; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse