Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway.
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.
Miyabayashi
Koutarou
K
The First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Maruyama
Muneharu
M
Yamada
Toru
T
Shinoda
Chie
C
Hounoki
Hiroyuki
H
Kanatani
Yukiko
Y
Shinoda
Kouichirou
K
Kawagishi
Yukio
Y
Miwa
Toshiro
T
Suzuki
Kensuke
K
Arai
Nobuki
N
Hayashi
Ryuji
R
Matsui
Shoko
S
Sugiyama
Eiji
E
Kobayashi
Masashi
M
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*
D018946:Chemokine CCL5; D016207:Cytokines; D048031:JNK Mitogen-Activated Protein Kinases; D007545:Isoproterenol