Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction.
The cell-to-cell interaction through binding of intercellular adhesion molecule (ICAM)-1 on monocytes to their ligands lymphocyte function-associated antigen (LFA)-1 on T-cells plays important roles in cytokine production and T-cell proliferation. Interleukin (IL)-18, which plasma levels are elevated in patients during acute rejection following organ transplantation, induces the expression of ICAM-1 on monocytes, production of interferon (IFN)-gamma and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Activation of the adenosine A(2A) receptor on during reperfusion of various tissues has been found to markedly reduce ischemia-reperfusion injury. In the present study, we examined the effect of adenosine at increasing concentrations ranging from 0.1 to 100 microM on the IL-18-enhanced expression of ICAM-1, production of IFN-gamma and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Adenosine inhibited the IL-18-initiated immune responses. The IC(50) values of adenosine for inhibition of the IL-18-enhanced ICAM-1 expression, IFN-gamma production and lymphocyte proliferation were 20 microM, respectively. The actions of adenosine depended on the stimulation of adenosine A(2A) receptor. An inhibitor of protein kinase A (PKA) at 100 microM inhibited the actions of adenosine, suggesting that PKA might be involved in the actions of adenosine. On the other hand, the stimulation of adenosine A(1) and A(3) receptor blocked the actions of adenosine A(2A) receptor stimulation. These results suggest that adenosine inhibits the immune responses during mixed lymphocyte reaction via adenosine A(2A) receptor.
Takahashi
Hideo Kohka
HK
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan.
Iwagaki
Hiromi
H
Hamano
Ryosuke
R
Kanke
Toru
T
Liu
Keyue
K
Sadamori
Hiroshi
H
Yagi
Takahito
T
Yoshino
Tadashi
T
Sendo
Toshiaki
T
Tanaka
Noriaki
N
Nishibori
Masahiro
M
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D016207:Cytokines; D020382:Interleukin-18; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine