Swennen Els L R, Bast Aalt, Dagnelie Pieter C
Department of Pharmacology and Toxicology, NUTRIM, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Biochem Biophys Res Commun. 2006 Sep 29;348(3):1194-9. doi: 10.1016/j.bbrc.2006.07.177. Epub 2006 Aug 4.
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.
我们最近发现，生理化合物ATP在脂多糖-植物血凝素（LPS-PHA）刺激的血液中能同时抑制肿瘤坏死因子-α（TNF-α）并刺激白细胞介素-10（IL-10）释放。本研究的目的是确定ATP对TNF-α和IL-10协同调节作用所涉及的机制。在存在选择性P2受体拮抗剂的情况下，用ATP孵育血液表明，ATP对IL-10释放的刺激作用被2-甲硫腺苷酸（2-MeSAMP，一种P2Y12/13受体拮抗剂）和PSB-0413（一种P2Y12受体拮抗剂）完全消除。另一方面，ATP对TNF-α释放的抑制作用被5'-腺苷酸（5'-AMPS，一种P2Y11受体拮抗剂）以及环磷酸腺苷（cAMP）激活的蛋白激酶A（PKA）抑制剂H-89完全逆转。ATP通过激活P2Y11协同抑制TNF-α释放以及通过激活P2Y12刺激IL-10释放，这意味着通过改变促炎和抗炎细胞因子之间的平衡来实现免疫调节的一种新方法。
