Effect of beta 2-adrenergic receptor stimulation on interleukin-18-induced intercellular adhesion molecule-1 expression and cytokine production.
beta-Adrenergic receptor (AR) agonists have been demonstrated to modulate the production of inflammatory mediators. Recent studies implied that beta 2-AR agonists might be useful for chronic inflammatory diseases caused by interleukin (IL)-18. In the present study, we found that norepinephrine, epinephrine, or isoproterenol down-regulated IL-18 (100 ng/ml)-induced intercellular adhesion molecule (ICAM)-1 expression on monocytes in a dose-dependent manner (10(-8)-10(-4) M), but did not effect B7.1 and B7.2 expression after 24-h incubation. The modulatory effect of these catecholamines on ICAM-1 expression was antagonized by beta 2-AR antagonist, but not by alpha 1-, alpha 2-, or beta 1-AR antagonist. beta 2-AR-selective agonists salbutanol and terbutaline down-regulated IL-18-induced ICAM-1 expression on monocytes, but alpha 1-, alpha 2-, or beta1-AR agonist had no effect. In the same manner, salbutanol and terbutaline as well as norepinephrine, epinephrine, and isoproterenol regulated the IL-18-induced cytokine production, including IL-12, tumor necrosis factor-alpha or interferon-gamma through the stimulation of beta 2-AR. Together with the previous finding that ICAM-1/lymphocyte function-associated antigen-1 interaction plays a crucial role in the IL-18-initiated cytokine network, the present study strongly suggested that the stimulation of beta 2-AR inhibited the IL-18-activated cytokine cascade through the inhibitory effect on ICAM-1 expression, contributing to finding a new method for clinical treatment.
Takahashi
Hideo Kohka
HK
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Morichika
Toshihiko
T
Iwagaki
Hiromi
H
Yoshino
Tadashi
T
Tamura
Ryuji
R
Saito
Shinnya
S
Mori
Shuji
S
Akagi
Tadaatsu
T
Tanaka
Noriaki
N
Nishibori
Masahiro
M
D000322:Adrenergic Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism* / Q000502:physiology
D000322:Adrenergic Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D016207:Cytokines; D020382:Interleukin-18; D018343:Receptors, Adrenergic, beta-2; D018799:Intercellular Adhesion Molecule-1