Beta2-adrenoceptor stimulation inhibits advanced glycation end products-induced adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells.
Cell-to-cell interaction through binding of intercellular adhesion molecule-1 (ICAM-1) and CD40 on monocytes to their ligands on T-cells plays crucial roles in cytokine production. Advanced glycation end products (AGEs) subtypes induce complications in diabetes. In a previous study, we found that glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) at 100 microg/ml induced the expressions of ICAM-1 and CD40 on monocytes and the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in human peripheral blood mononuclear cells. beta(2)-adrenoceptor stimulation has been demonstrated to modulate the production of inflammatory mediators. In the present study, we found that norepinephrine, epinephrine and isoproterenol inhibited AGE-2- and AGE-3-induced adhesion expression and cytokine production in a concentration-dependent manner. The action of these catecholamines was antagonized by beta(2)-adrenoceptor antagonist, but not by alpha(1)-, alpha(2)- and beta(1)-adrenoceptor antagonist. beta(2)-adrenoceptor agonists, salbutanol and terbutaline inhibited AGE-2- and AGE-3-induced adhesion expression and cytokine production, but alpha(1)-, alpha(2)- and beta(1)-adrenoceptor agonist had no effect, indicating that the stimulation of beta(2)-adrenoceptor might improve AGEs-initiated complications in diabetes.
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan.
Hideo Kohka
HK
Takahashi
Shuji
S
Mori
Keyue
K
Liu
Hidenori
H
Wake
Jiyong
J
Zhang
Rui
R
Liu
Tadashi
T
Yoshino
Masahiro
M
Nishibori
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D004837:Epinephrine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007545:Isoproterenol / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D017127:Glycation End Products, Advanced; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine