Abstract
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.
Footnotes
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This study was supported in part by a grant from Japan Society for Promotion of Science (BSAR-521/0003815; to M.N.), grants for promotion of research from Okayama University (21, to M.N.; 26, to T.A.), and a grant from the Okayama Medical Foundation (to H.K.T.).
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DOI: 10.1124/jpet.102.042622
- Abbreviations:
- IL
- interleukin
- Th
- T helper
- NK
- natural killer
- IFN
- interferon
- ICAM
- intercellular adhesion molecule
- AR
- adrenergic receptor
- MS
- multiple sclerosis
- RA
- rheumatoid arthritis
- LFA
- lymphocyte function-associated antigen
- PBMC
- peripheral blood mononuclear cell
- FITC
- fluorescein isothiocyanate
- mAb
- monoclonal antibody
- CMC
- class-matched control
- Ab
- antibody
- TNF
- tumor necrosis factor
- ELISA
- enzyme-linked immunosorbent assay
- Received August 6, 2002.
- Accepted October 30, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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