title: Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway.
abstract: It has been reported that beta2-agonists may potentially exert some anti-inflammatory action in addition to bronchodilation that may contribute to their beneficial effects on asthma control. Bronchial epithelial cells are well known to respond to a range of stimuli by producing various biologically active mediators that can influence airway inflammation. RANTES (regulated on activation, normal T cells expressed and secreted) plays an important role in the pathophysiology of airway inflammation of asthmatics through its chemotactic activity for eosinophils. In this study, the authors investigated whether cytokine-induced RANTES release from BEAS-2B human bronchial epithelial cells could be modulated by beta-agonist isoproterenol (ISO). The possible involvement of c-jun N-terminal kinase (JNK) pathway was also studied. Combination of tumor necrosis factor-alpha and interleukin-1beta (cytokine mix) increased RANTES release from BEAS-2B cells and stimulated JNK activity. Similar to JNK inhibitor SP600125, ISO inhibited not only the production of RANTES but also the activation of JNK pathway in cytokine mix-stimulated BEAS-2B cells. The effect of ISO was mediated by the beta2-adrenoceptor, since it was blocked by ICI 118,551, a selective beta2-receptor antagonist, but not by atenolol, a selective beta1-receptor antagonist. Adenylyl cyclase activator forskolin reproduced the effects of ISO. Isoproterenol was found to inhibit the release of RANTES from the human bronchial epithelial cells, at least in part, through the inhibition of JNK signaling pathway.
authors.affiliation: The First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Koutarou
authors.initials: K
authors.lastname: Miyabayashi
authors.forename: Muneharu
authors.initials: M
authors.lastname: Maruyama
authors.forename: Toru
authors.initials: T
authors.lastname: Yamada
authors.forename: Chie
authors.initials: C
authors.lastname: Shinoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hounoki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanatani
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Shinoda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kawagishi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Miwa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nobuki
authors.initials: N
authors.lastname: Arai
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hayashi
authors.forename: Shoko
authors.initials: S
authors.lastname: Matsui
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugiyama
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D002460:Cell Line; D018946:Chemokine CCL5 / Q000378:metabolism*; D016207:Cytokines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D048031:JNK Mitogen-Activated Protein Kinases; D007545:Isoproterenol