RT Journal Article
SR Electronic
T1 Effect of β2-Adrenergic Receptor Stimulation on Interleukin-18-Induced Intercellular Adhesion Molecule-1 Expression and Cytokine Production
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 634
OP 642
DO 10.1124/jpet.102.042622
VO 304
IS 2
A1 Hideo Kohka Takahashi
A1 Toshihiko Morichika
A1 Hiromi Iwagaki
A1 Tadashi Yoshino
A1 Ryuji Tamura
A1 Shinnya Saito
A1 Shuji Mori
A1 Tadaatsu Akagi
A1 Noriaki Tanaka
A1 Masahiro Nishibori
YR 2003
UL http://jpet.aspetjournals.org/content/304/2/634.abstract
AB β-Adrenergic receptor (AR) agonists have been demonstrated to modulate the production of inflammatory mediators. Recent studies implied that β2-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 β2-AR antagonist, but not by α1-, α2-, or β1-AR antagonist. β2-AR-selective agonists salbutanol and terbutaline down-regulated IL-18-induced ICAM-1 expression on monocytes, but α1-, α2-, or β1-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-α or interferon-γ through the stimulation of β2-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 β2-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. The American Society for Pharmacology and Experimental Therapeutics