Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Dr., Madison, WI, 53706, USA.
Purinergic Signal. 2008 Mar;4(1):73-8. doi: 10.1007/s11302-008-9095-1. Epub 2008 Feb 8.
In this study we evaluated the functionality and inflammatory effects of P2Y14 receptors in murine N9 microglia. The selective P2Y14 receptor agonist UDP-glucose (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.
在这项研究中，我们评估了 P2Y14 受体在小鼠 N9 小胶质细胞中的功能和炎症效应。来源于微生物的 P2Y14 受体选择性激动剂 UDP-葡萄糖（UDPG）剂量依赖性地刺激环氧化酶-2 和诱导型一氧化氮合酶的表达，并增强细菌脂多糖对一氧化氮产生的作用。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，合成 UDPG 也没有可检测到的促炎作用，尽管 P2Y14 受体在 N9 小胶质细胞中均有表达和功能。虽然合成 UDPG 降低了磷酸化环腺苷酸反应元件结合蛋白的水平，这种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 的促炎作用独立于 P2Y14 受体，并暗示 UDPG 制剂中微生物来源的污染物可能参与了观察到的炎症反应。
