The inflammatory effects of UDP-glucose in N9 microglia are not mediated by P2Y14 receptor activation
The inflammatory effects of UDP-glucose in N9 microglia are not mediated by P2Y14 receptor activation
复制标题
DOI：
10.1007/s11302-008-9095-1
复制
发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Watters, Jyoti J.
中科院分区：
文献类型：
--
作者：
Brautigam, Vielska M.;Dubyak, George R.;Watters, Jyoti J.
在本研究中，我们评估了P2Y14受体在小鼠N9小胶质细胞中的功能和炎症作用。来自微生物源的选择性P2Y14受体激动剂UDPglucose （UDPG）剂量依赖性地刺激了环氧化酶-2和诱导型一氧化氮合酶的表达，并增强了细菌脂多糖对一氧化氮生成的影响。然而，另一种选择性P2Y14受体激动剂，udp -半乳糖，无论是单独使用还是与脂多糖联合使用，都不会影响这些终点。有趣的是，尽管P2Y14受体在N9小胶质细胞中均有表达和功能，但合成的UDPG也没有可检测到的促炎作用。虽然合成的UDPG降低了磷酸化环AMP反应元件结合蛋白的水平，这一作用被百日咳毒素阻断，但微生物来源的UDPG的促炎作用对百日咳毒素不敏感。这些数据表明，微生物来源的UDPG的促炎作用不依赖于P2Y14受体，这意味着UDPG制备中的微生物来源污染物可能参与了观察到的炎症作用。
In this study we evaluated the functionality and inflammatory effects of P2Y14 receptors in murine N9 microglia. The selective P2Y14 receptor agonist UDPglucose (UDPG) derived from microbial sources dose dependently stimulated expression of cyclooxygenase-2 and inducible nitric oxide synthase, and potentiated the effects of bacterial lipopolysaccharide on nitric oxide production. However, another selective P2Y14 receptor agonist, UDP-galactose, did not affect these endpoints either alone or in combination with lipopolysaccharide. Interestingly, synthetic UDPG also had no detectable pro-inflammatory effects, although P2Y14 receptors are both expressed and functional in N9 microglia. While synthetic UDPG decreased levels of phosphorylated cyclic AMP response element binding protein, an effect that was blocked by pertussis toxin, the pro-inflammatory effects of microbial-derived UDPG were insensitive to pertussis toxin. These data suggest that the pro-inflammatory effects of microbial-derived UDPG are independent of P2Y14 receptors and imply that microbial-derived contaminants in the UDPG preparation may be involved in the observed inflammatory effects.