Therapeutic administration of Budesonide ameliorates allergen-induced airway remodelling.
BACKGROUND
Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti-inflammatory activity, there are limited effects on the structural changes in the lung tissue.


OBJECTIVE
We have used a mouse model of prolonged allergen challenge that exhibits many of the salient features of airway remodelling in order to investigate the anti-remodelling effects of Budesonide.


METHODS
Treatment was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation and hyper-reactivity.


RESULTS
Budesonide administration reduced airway hyper-reactivity and leukocyte infiltration in association with a decrease in production of the Th2 mediators, IL-4, IL-13 and eotaxin-1. A reduction in peribronchiolar collagen deposition and mucus production was observed. Moreover, our data show for the first time that, Budesonide treatment regulated active transforming growth factor (TGF)-beta signalling with a reduction in the expression of pSmad 2 and the concomitant up-regulation of Smad 7 in lung tissue sections.


CONCLUSIONS
Therefore, we have determined that administration of Budesonide modulates the progression of airway remodelling following prolonged allergen challenge via regulation of inflammation and active TGF-beta signalling.
McMillan
S J
SJ
Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine Imperial College, London SW7 2AZ, UK.
Xanthou
G
G
Lloyd
C M
CM
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D019819:Budesonide / Q000627:therapeutic use*; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D007091:Image Processing, Computer-Assisted; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009093:Mucus; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000485:Allergens; D018927:Anti-Asthmatic Agents; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D019819:Budesonide; D003094:Collagen