Regulation of purinergic signaling by prostaglandin E2 in murine macrophages
Regulation of purinergic signaling by prostaglandin E2 in murine macrophages
复制标题
DOI：
10.1254/jphs.08087fp
复制
发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Matsuoka, Isao
中科院分区：
文献类型：
--
作者：
Ito, Masaaki;Matsuoka, Isao
细胞外核苷酸是组织损伤的主要信号，与炎症部位的前列腺素等各种化学介质共同作用。我们研究了前列腺素E-2(PGE(2))是否影响小鼠J774巨噬细胞的嘌呤能信号。J774细胞表达4种不同的嘌呤受体mRNAs：离子型P2X(4)和P2X(7)受体以及G蛋白偶联的P2Y(2)和P2Y(6)受体。通过检测Fura-2负载细胞内钙离子浓度([Ca~(2+)](I))，证实了这些嘌呤受体亚型介导的功能反应。因此，低浓度(10 MU M)的ATP(P2Y(2)激动剂)和UDP(P2Y(6)激动剂)以磷脂酶C(PLC)依赖的方式引起钙瞬变，而P2X(7)激动剂苯甲酰苯甲酰-ATP(BzATP，500 mU M)引起[Ca~(2+)](I)持续升高。此外，P2X(4)-受体通道激动剂伊维菌素可增强ATP诱导的[Ca~(2+)](I)升高。PGE(2)抑制ATP和UDP诱导的[Ca~(2+)](I)升高，但不影响BzATP诱导的持续性[Ca~(2+)](I)升高。UDP或BzATP刺激J774细胞可增加巨噬细胞炎性肽-α(MIP-α)的产生。PGE(2)可抑制UDP诱导的MIP-α产生，但不能抑制BzATP诱导的MIP-α产生。这些结果表明，巨噬细胞中的嘌呤能信号是由PGE(2)以亚型特异性的方式调节的。PGE(2)不同的抑制作用和不同的嘌呤受体功能可能与其抗炎作用有关。
Extracellular nucleotides are primary signals for tissue injury, acting together with various chemical mediators Such as prostanoids at the Inflammatory site. We investigated whether prostaglandin E-2 (PGE(2)) affects purinergic signaling in murine J774 macrophages. J774 cells expressed four different purinoceptor mRNAs: the ionotropic P2X(4) and P2X(7) receptors and G-protein-coupled P2Y(2) and P2Y(6) receptors. Functional responses mediated by these purinoceptor subtypes were confirmed by measurement of intracellular Ca2+ concentration ([Ca2+](i)) in fura-2-loaded cells. Thus, low concentrations (10 mu M) of ATP (P2Y(2) agonist) and UDP (P2Y(6) agonist) evoked Ca2+ transient in a phospholipase C (PLC)-dependent manner, whereas the P2X(7) agonist benzoylbenzoyl-ATP (BzATP, 500 mu M) caused a sustained rise in [Ca2+](i). Furthermore, ivermectin, an activator of the P2X(4)-receptor channel, enhanced the ATP-induced [Ca2+](i) elevation. PGE(2) inhibited ATP- and UDP-induced [Ca2+](i) elevation, without affecting the BzATP-induced sustained [Ca2+](i) elevation. Stimulation or J774 cells by UDP or BzATP increased the production of macrophage inflammatory peptide-alpha (MIP-alpha). PGE(2) abolished the UDP-induced MIP-alpha production, but not the BzATP-induced one. These results demonstrate that purinergic signalings in macrophages were regulated by PGE(2) in a subtype-specific manner. The different inhibitory effects oil distinct purinoceptor functions may be related to the anti-inflammatory property of PGE(2).