Mechanisms of asthma and allergic inflammationIL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts
Section snippets
Cell culture
The human normal lung fibroblasts CCD-8Lu were purchased from American Type Culture Collection (Rockville, Md) and studied at passages 4-7. Cells were cultured in Dulbecco's modified Eagle Medium containing 100 U/mL penicillin, 100 μg/mL streptomycin (GIBCO, Grand Island, NY), and 10% FCS (HyClone Laboratories, Logan, Utah). Unless otherwise specified, fibroblasts were seeded in 6-well plates and grown to confluence. Cells were washed in PBS and serum-deprived for 24 hours before stimulation
Expression and regulation of a receptor for IL-17E, IL-17BR, in human lung fibroblasts
By using cultured fibroblasts obtained from human lung, we demonstrated a constitutive expression of IL-17BR, as shown by immunofluorescent staining using a specific mAb directed against the extracellular domain of the receptor (Fig 1, A, left panel). No staining was observed when an irrelevant isotype-matched antibody was used (Fig 1, A, right panel).
The presence of IL-17BR in fibroblasts was confirmed by Western blot analysis. The mAb detected a 56-kd protein corresponding to the full length
Discussion
The recently described cytokine IL-17E may play a role in allergic inflammation and remodeling of the airways. To date, however, very little is known about its involvement in human disease, particularly in asthma. This study demonstrates for the first time the constitutive expression of a receptor for IL-17E, IL-17BR, in human primary lung fibroblasts, and supports a role for IL-17E in allergic airway inflammation.
We show that IL-17E stimulates the production of several mediators known to favor
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Supported by a grant from the Canadian Institutes of Health Research. Dr Létuvé is funded by a fellowship from the Canadian Lung Association and Merck Frosst Canada.