Article

Therapeutic administration of Budesonide ameliorates allergen-induced airway remodelling

Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine Imperial College, London SW7 2AZ, UK.
Clinical & Experimental Allergy (Impact Factor: 4.32). 04/2005; 35(3):388-96. DOI: 10.1111/j.1365-2222.02193.x
Source: PubMed

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

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    • "However, none of the available drugs today significantly affects or reverses the airway wall remodelling. On the contrary, there is evidence that glucocorticoids may worsen airway remodelling under certain conditions in humans at least in vitro (Chakir et al., 2003; de Kluijver et al., 2005; Goulet et al., 2007), but not in animal models (McMillan et al., 2005). Such species-specific differences may be explained by a feedback mechanism between collagens and glucocorticoid signalling (Bonacci et al., 2003; Goulet et al., 2007). "
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    • "It has indeed been found that glucocorticosteroids can attenuate the fibrotic process involved in airway remodeling. In particular, using a mouse model of airway remodeling induced by repeated exposures to allergen challenge, McMillan et al. (2005) recently showed that BUD reduced subepithelial collagen deposition by interfering with TGF-b1 signaling via a decrease in the expression of phosphorylated Smad2, associated with the induction of its inhibitor Smad7. Moreover, it has been shown that glucocorticoid receptors are able to interact with Smad3, a TGF-b-activated DNA binding protein, thus inactivating its transcriptional function (Song et al., 1999). "
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