title: Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction.
abstract: 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.
authors: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan.
authors: Hideo Kohka
authors: HK
authors: Takahashi
authors: Hiromi
authors: H
authors: Iwagaki
authors: Ryosuke
authors: R
authors: Hamano
authors: Toru
authors: T
authors: Kanke
authors: Keyue
authors: K
authors: Liu
authors: Hiroshi
authors: H
authors: Sadamori
authors: Takahito
authors: T
authors: Yagi
authors: Tadashi
authors: T
authors: Yoshino
authors: Toshiaki
authors: T
authors: Sendo
authors: Noriaki
authors: N
authors: Tanaka
authors: Masahiro
authors: M
authors: Nishibori
mesh_terms: 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*
chemical_list: 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