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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8001-8013
Number of pages13
JournalMolecular Neurobiology
Volume55
Issue number10
DOIs
Publication statusPublished - 2018 Oct 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience (miscellaneous)

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