Purinergic receptors involved in the immunomodulatory effects of ATP in human blood.
We recently showed that the physiological compound ATP simultaneously inhibited TNF-alpha and stimulated IL-10 release in LPS-PHA stimulated blood. The purpose of the present study was to determine the mechanism involved in the concerted modulatory effect of ATP on TNF-alpha and IL-10. Incubation of blood with ATP in the presence of selective P2 receptor antagonists showed that the stimulatory effect of ATP on IL-10 release was completely annihilated by both 2-MeSAMP (a P2Y12/13 receptor antagonist) and PSB-0413 (a P2Y12 receptor antagonist). On the other hand, the inhibitory effect of ATP on TNF-alpha release was completely reversed by 5'-AMPS (a P2Y11 receptor antagonist) as well as by H-89, an inhibitor of cAMP-activated PKA. The concerted inhibition by ATP of TNF-alpha release via P2Y11 activation and stimulation of IL-10 release via P2Y12 activation implicates a novel approach towards immunomodulation by altering the balance among pro- and anti-inflammatory cytokines.
Swennen
Els L R
EL
Department of Pharmacology and Toxicology, NUTRIM, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. e.swennen@farmaco.unimaas.nl
Bast
Aalt
A
Dagnelie
Pieter C
PC
D000255:Adenosine Triphosphate / Q000097:blood* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D018836:Inflammation Mediators / Q000097:blood* / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D011983:Receptors, Purinergic / Q000097:blood* / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; C109734:P2RY11 protein, human; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000255:Adenosine Triphosphate