Physiological Concentration of Prostaglandin E2 Exerts Anti-inflammatory Effects by Inhibiting Microglial Production of Superoxide Through a Novel Pathway

Shih Heng Chen, Yueh Feng Sung, Esteban A. Oyarzabal, Yu Mei Tan, Jeremy Leonard, Mingri Guo, Shuo Li, Qingshan Wang, Chun Hsien Chu, Shiou Lan Chen, Ru Band Lu, Jau Shyong Hong

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

摘要

This study investigated the physiological regulation of brain immune homeostasis in rat primary neuron-glial cultures by sub-nanomolar concentrations of prostaglandin E2 (PGE2). We demonstrated that 0.01 to 10 nM PGE2 protected dopaminergic neurons against LPS-induced neurotoxicity through a reduction of microglial release of pro-inflammatory factors in a dose-dependent manner. Mechanistically, neuroprotective effects elicited by PGE2 were mediated by the inhibition of microglial NOX2, a major superoxide-producing enzyme. This conclusion was supported by (1) the close relationship between inhibition of superoxide and PGE2-induced neuroprotective effects; (2) the mediation of PGE2-induced reduction of superoxide and neuroprotection via direct inhibition of the catalytic subunit of NOX2, gp91phox, rather than through the inhibition of conventional prostaglandin E2 receptors; and (3) abolishment of the neuroprotective effect of PGE2 in NOX2-deficient cultures. In summary, this study revealed a potential physiological role of PGE2 in maintaining brain immune homeostasis and protecting neurons via an EP receptor-independent mechanism.

原文English
頁(從 - 到)8001-8013
頁數13
期刊Molecular Neurobiology
55
發行號10
DOIs
出版狀態Published - 2018 10月 1

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學
  • 神經科學(雜項)

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