title: Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity.
abstract: Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.
authors.affiliation: The First Dept of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: E
authors.initials: E
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Masubuchi
authors.forename: A
authors.initials: A
authors.lastname: Takamizawa
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Isumi
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007424:Intracellular Fluid / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017265:Procaterol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D018946:Chemokine CCL5; D007375:Interleukin-1; D016209:Interleukin-8; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013806:Theophylline; D000242:Cyclic AMP; D017265:Procaterol