Original Articles: Mechanisms of AllergyIL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines☆,☆☆
Section snippets
Subjects
Eleven asthmatic subjects fulfilling the American Thoracic Society criteria for asthma17 were recruited (Table I). Of these, 6 patients agreed to undergo BAL and sputum induction. Sputum induction was done first; BAL was done 1 week later. The symptoms of these patients were controlled by regular use of inhaled selective β2-agonists only. Six of the patients with mild asthma were atopic, inasmuch as they had positive skin reactions to at least 1 common allergen. All subjects were nonsmokers or
RT-PCR
Fibroblasts were seeded in 6-well plates, grown to confluence, and stimulated with recombinant human IL-17 (rhIL-17; 25 ng/mL) in the presence or absence of dexamethasone (Dex; 10–7 mol/L) for 24 hours. Optimal concentrations of Dex and IL-17 were selected according to a preliminary concentration-response curve. Cell viability was not affected by Dex as assessed by the Trypan blue exclusion method. Dex was used in co-incubation with rhIL-17 in culture medium on bronchial fibroblasts. Controls
Expression of IL-17 immunoreactivity in sputum and BAL fluid
Cells positive for IL-17 immunoreactivity were found in sputum and BAL fluid of both asthmatic and normal control subjects. The numbers of cells expressing IL-17 immunoreactive protein were significantly higher in sputum (P < .001) and BAL (P < .005) recovered from asthmatic subjects than in sputum and BAL recovered from nonasthmatic controls (Fig 1).
Discussion
In the present study, we demonstrated that IL-17 is upregulated in asthma, that eosinophils also are cellular sources of its production, and that IL-17 increases synthesis of IL-6 and IL-11 by bronchial fibroblasts derived from bronchial biopsies of asthmatic subjects.
Several reports have demonstrated that IL-17 has the capacity to induce the production of other cytokines from structural cells and to enhance the surface expression of intracellular adhesion molecule-1.4, 5 Chabaud et al15
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Cited by (0)
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Supported in part by Medical Research Council Canada (MT-13273), Astra Canada, and the Chair de Pneumologie de la Fondation J. Bégin. S. Molet is the recipient of a Canadian Lung Association/Canadian Thoracic Society and Merck-Frosst fellowship. Q. Hamid and J. Chakir are the recipients of a Chercheur-Boursier award from the Fonds de la Recherche en Santé du Québec.
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Reprint requests: Jamila Chakir, PhD, Centre de Recherche, Hôpital Laval, 2725 Chemin Sainte-Foy, Sainte-Foy (QC), G1V 4G5 Canada.