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

Molecular Neurobiology
Shih-Heng ChenJau-Shyong Hong

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.

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Citations

Oct 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Emma L B SoldnerBjörn Bauer
Oct 3, 2020·Molecular Neurobiology·Gabriela Cruz-Carrillo, Alberto Camacho-Morales
Nov 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hiromichi Fujino

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Methods Mentioned

BETA
ELISA
enzyme-linked immunosorbent assay

Software Mentioned

Prism
GraphPad
AlphaImager 3400
Molecular Operating Environment ( MOE

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