- Title
- Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma
- Creator
- Herbert, C.; Hettiaratchi, A.; Webb, D. C.; Thomas, P. S.; Foster, P. S.; Kumar, R. K.
- Relation
- Clinical and Experimental Allergy Vol. 38, Issue 5, p. 847-856
- Relation
- http://www3.interscience.wiley.com/journal/119410150/abstract
- Publisher
- Blackwell Publishing
- Resource Type
- journal article
- Date
- 2008
- Description
- Background: In a mouse model of mild chronic asthma, both inflammation and remodelling can be suppressed by dexamethasone (a glucocorticoid) and roflumilast (a selective phosphodiesterase-4 inhibitor). Objective: To better understand the underlying molecular mechanisms, we investigated the effects of treatment on airway expression of inflammation-related cytokines, as well as on epithelial expression of growth factors. Methods: BALB/c mice systemically sensitized to ovalbumin were challenged with aerosolized antigen for 6 weeks and treated with roflumilast or dexamethasone during the final 2 weeks. Expression of mRNA, for a variety of cytokines and growth factors, was assessed in selectively dissected proximal airways or in airway epithelium obtained by laser capture microdissection. Results: In the airway wall of vehicle-treated challenged animals, there was significantly elevated expression of mRNA for a variety of pro-inflammatory and T helper type 2 cytokines, as well as for IFN-γ. All these cytokines were suppressed by dexamethasone. Treatment with roflumilast reduced expression of IL-17A, TNF-α, granulocyte-macrophage colonystimulating factor and IL-6, but did not inhibit other cytokines. Both drugs suppressed the enhanced expression of mRNA for growth factors such as TGF-β1 and FGF-2 in airway epithelium. Conclusions: Whereas dexamethasone non-specifically inhibits numerous mediators involved in inflammation and the immune response, roflumilast selectively inhibits a subset of proinflammatory cytokines and growth factors. These mediators and/or the cells that produce them may have critical roles in the pathogenesis of the lesions of chronic asthma.
- Subject
- airway inflammation; airway remodelling; cytokines; phosphodiesterase-4 inhibitors; Th17 cells
- Identifier
- http://hdl.handle.net/1959.13/41448
- Identifier
- uon:4804
- Identifier
- ISSN:0954-7894
- Language
- eng
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