Blockade of murine T cell activation by antagonists of P2Y6 and P2X7 receptors.
Extracellular nucleotides and their metabolites activate ionotropic P2X and metabotropic P2Y receptors on the surface of various types of cells. Here, we investigated the involvement of P2X and P2Y receptor-mediated signaling in TCR-dependent T cell activation. Murine T cells were activated by stimulation of TCR, and both CD25 expression and interleukin (IL)-2 production were observed in activated T cells. Ecto-nucleotidase apyrase and P2Y6 antagonist MRS2578 significantly blocked the increases of both CD25 expression and IL-2 production, and P2X7 antagonists A438079 and oxidized ATP inhibited IL-2 production rather than CD25 expression, suggesting the involvement of P2Y6 and P2X7 receptors in different processes of T cell activation. MRS2578 also blocked TCR-dependent elevation of cytosolic Ca2+ in T cells. The P2X7 and P2Y6 receptors were expressed in murine CD4 T cells. In conclusion, our results indicate that activation of P2Y6 and P2X7 receptors contributes to T cell activation via TCR.
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. tsukim@rs.noda.tus.ac.jp
Mitsutoshi
M
Tsukimoto
Akihiro
A
Tokunaga
Hitoshi
H
Harada
Shuji
S
Kojima
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013777:Tetrazoles / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; D017879:Isothiocyanates; C541384:N,N''-1,4-butanediylbis(N'-(3-isothiocyanatophenyl))thiourea; C546469:P2rx7 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D011948:Receptors, Antigen, T-Cell; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles; C099845:purinoceptor P2Y6; D013890:Thiourea; D002118:Calcium