Induction of airway remodeling of nasal mucosa by repetitive allergen challenge in a murine model of allergic rhinitis.
BACKGROUND
Although many studies regarding airway remodeling in asthma have been reported, only a few studies have investigated airway remodeling in allergic rhinitis.


OBJECTIVE
To determine whether repetitive allergen challenge could induce airway remodeling in the nose and evaluate the effect of steroids using a murine model of allergic rhinitis.


METHODS
To develop a mouse model of airway remodeling, ovalbumin-sensitized mice were repeatedly exposed to inhaled ovalbumin administration twice a week for 1 month and 3 months. Matched control mice were challenged with phosphate-buffered saline, and the treatment group received intraperitoneal dexamethasone injection. Trichrome, periodic acid-Schiff, hematoxylin-eosin, and immunohistochemical staining against matrix metalloproteinase 9 and tissue inhibitors of metalloproteinase 1 were performed to nasal and lung tissues, and the level of transforming growth factor beta in the nasal lavage fluid was analyzed.


RESULTS
Repetitive ovalbumin challenge for 3 months induced circumferential peribronchial fibrosis in the lung. In the nose, subepithelial fibrosis, increased matrix metalloproteinase 9 and tissue inhibitors of metalloproteinase 1 expression, goblet cell hyperplasia, and submucous gland hypertrophy were observed compared with the control group. Features of airway remodeling were more prominent in the lung tissue. Administration of dexamethasone significantly inhibited these histologic changes.


CONCLUSIONS
Airway remodeling associated with long-term allergen challenge can occur in the nasal mucosa and the lung. Steroid treatment prevents airway inflammation in response to acute allergen challenge, as well as airway remodeling by long-term allergen challenge.
Lim
Yune Sung
YS
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.
Won
Tae-Bin
TB
Shim
Woo Sub
WS
Kim
Yong Min
YM
Kim
Jeong-Whun
JW
Lee
Chul Hee
CH
Min
Yang-Gi
YG
Rhee
Chae-Seo
CS
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005355:Fibrosis / Q000276:immunology / Q000517:prevention & control; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000485:Allergens; D000893:Anti-Inflammatory Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D010047:Ovalbumin; D020780:Matrix Metalloproteinase 9