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Regulation of TNF‐α‐induced eotaxin release from cultured human airway smooth muscle cells by β 2 ‐agonists and corticosteroids
Author(s) -
PANG LINHUA,
KNOX ALAN J.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0103com
Subject(s) - rolipram , eotaxin , eosinophil , forskolin , phosphodiesterase , pharmacology , agonist , salmeterol , eosinophilia , salbutamol , phosphodiesterase inhibitor , endocrinology , tumor necrosis factor alpha , cytokine , medicine , corticosteroid , chemistry , asthma , receptor , biochemistry , enzyme
Eotaxin is a potent eosinophil chemoattractant that contributes to the eosinophilia seen in asthma and other allergic disorders. Recent studies have identified human airway smooth muscle (HASM) as a rich source of eotaxin, but the factors regulating its production are poorly understood. Here we describe for the first time that β 2 ‐agonists can inhibit cytokineinduced eotaxin release. We found that TNF‐α stimulated eotaxin release (assayed by ELISA) from HASM cells and that the release was partially inhibited by salbutamol and salmeterol. The effect of β 2 ‐agonists was mimicked by forskolin and 8‐bromo‐cAMP and potentiated by the cAMP‐dependent phosphodiesterase inhibitor rolipram, suggesting that it is cAMP dependent. We also found that the cAMP inhibition was likely at the transcription stage, although experiments with the PKA inhibitors H‐89 and Rp‐cAMP or the PKG inhibitor KT5823 suggested that none of these kinases was involved. Partial inhibition of eotaxin release was also seen with the corticosteroids dexamethasone and fluticasone. The combined use of β 2 ‐agonists, rolipram, and steroids abolished TNF‐α‐induced eotaxin release. These results suggest that the combination of a β 2 ‐agonist, PDE inhibitor, and a corticosteroid may have additive beneficial effects in the treatment of the eosinophilia associated with asthma and other allergic diseases—Pang, L., Knox, A. J. Regulation of TNF‐α‐induced eotaxin release from cultured human airway smooth muscle cells by β 2 ‐agonists and corticosteroids. FASEB J. 15, 261–269 (2001)