Effect of beta2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1, B7, and CD40 expression in mixed lymphocyte reaction.
BACKGROUND
The plasma interleukin (IL)-18 level is elevated in acute rejection after organ transplantation. Although beta2-adrenergic receptor (AR) agonists suppress the rejection of organ and tissue transplants, little is known about their action mechanisms. We examined the effects of endogenous catecholamines and beta2-AR agonists on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) in human mixed lymphocyte reaction (MLR) and in an in vitro model of acute rejection in the presence or absence of IL-18.


METHODS
ICAM-1, B7.1 B7.2, CD40, and CD40L expression on monocytes was measured by flow cytometry, and the production of interferon (IFN)-gamma and IL-12 was determined by enzyme-linked immunosorbent assay. Lymphocytes proliferation in MLR was measured by [3H]-thymidine uptake. The relevant AR subtypes were characterized using subtype-selective agonists and antagonists.


RESULTS
beta2-AR agonists inhibited the expression of ICAM-1 and CD40 during MLR in the absence of IL-18. Among IL-18-induced expression of ICAM-1, B7.1, B7.2, CD40, and CD40L, beta2-AR agonists inhibited ICAM-1 and CD40 expression. beta2-AR agonists prevented the production of IFN-gamma and IL-12 in the presence of IL-18 but had no effect in the absence of IL-18. beta2-AR agonists inhibited lymphocyte proliferation in IL-18-treated MLR.


CONCLUSIONS
We found that beta2-AR agonists strongly inhibited the expression of ICAM-1 and CD40, irrespective of the presence or absence of IL-18, which is different from that of histamine and prostaglandin E2.
Tamura
Ryuji
R
Department of Gastroenterological Surgery and Transplant, Okayama University Graduate School of Medicine and Dentistry, Okayama City, Japan.
Takahashi
Hideo K
HK
Iwagaki
Hiromi
H
Yagi
Takahito
T
Mori
Shuji
S
Yoshino
Tadashi
T
Nishibori
Masahiro
M
Tanaka
Noriaki
N
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000187:drug effects / Q000378:metabolism*; D019013:CD40 Antigens / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D018448:Models, Immunological; D011994:Recombinant Proteins / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D018122:B7-1 Antigen; D019013:CD40 Antigens; D020382:Interleukin-18; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma