Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction

Hideo Kohka Takahashi, Hiromi Iwagaki, Ryosuke Hamano, Toru Kanke, Keyue Liu, Hiroshi Sadamori, Takahito Yagi, Tadashi Yoshino, Toshiaki Sendo, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticle

17 Citations (Scopus)

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)-γ and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Activation of the adenosine A2A 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 μM on the IL-18-enhanced expression of ICAM-1, production of IFN-γ and IL-12 and lymphocyte proliferation during human mixed lymphocyte reaction. Adenosine inhibited the IL-18-initiated immune responses. The IC50 values of adenosine for inhibition of the IL-18-enhanced ICAM-1 expression, IFN-γ production and lymphocyte proliferation were 20 μM, respectively. The actions of adenosine depended on the stimulation of adenosine A2A receptor. An inhibitor of protein kinase A (PKA) at 100 μM inhibited the actions of adenosine, suggesting that PKA might be involved in the actions of adenosine. On the other hand, the stimulation of adenosine A1 and A3 receptor blocked the actions of adenosine A2A receptor stimulation. These results suggest that adenosine inhibits the immune responses during mixed lymphocyte reaction via adenosine A2A receptor.

Original languageEnglish
Pages (from-to)204-210
Number of pages7
JournalEuropean Journal of Pharmacology
Volume564
Issue number1-3
DOIs
Publication statusPublished - Jun 14 2007

Fingerprint

Mixed Lymphocyte Culture Test
Purinergic P1 Receptors
Adenosine
Adenosine A2A Receptors
Interleukin-18
Intercellular Adhesion Molecule-1
Interferons
Lymphocytes
Interleukin-12
Cyclic AMP-Dependent Protein Kinases
Monocytes
Adenosine A3 Receptors
T-Lymphocytes
Adenosine A1 Receptors
Lymphocyte Function-Associated Antigen-1
Organ Transplantation
Reperfusion Injury
Cell Communication
Inhibitory Concentration 50
Reperfusion

Keywords

  • Adenosine
  • Interleukin-18
  • Monocyte

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction. / Takahashi, Hideo Kohka; Iwagaki, Hiromi; Hamano, Ryosuke; Kanke, Toru; Liu, Keyue; Sadamori, Hiroshi; Yagi, Takahito; Yoshino, Tadashi; Sendo, Toshiaki; Tanaka, Noriaki; Nishibori, Masahiro.

In: European Journal of Pharmacology, Vol. 564, No. 1-3, 14.06.2007, p. 204-210.

Research output: Contribution to journalArticle

Takahashi HK, Iwagaki H, Hamano R, Kanke T, Liu K, Sadamori H et al. Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction. European Journal of Pharmacology. 2007 Jun 14;564(1-3):204-210. https://doi.org/10.1016/j.ejphar.2007.02.005
Takahashi, Hideo Kohka ; Iwagaki, Hiromi ; Hamano, Ryosuke ; Kanke, Toru ; Liu, Keyue ; Sadamori, Hiroshi ; Yagi, Takahito ; Yoshino, Tadashi ; Sendo, Toshiaki ; Tanaka, Noriaki ; Nishibori, Masahiro. / Effect of adenosine receptor subtypes stimulation on mixed lymphocyte reaction. In: European Journal of Pharmacology. 2007 ; Vol. 564, No. 1-3. pp. 204-210.
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AU - Yagi, Takahito

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