Prostaglandin E2 production in astrocytes: Regulation by cytokines, extracellular ATP, and oxidative agents

J. Xu, M. Chalimoniuk, Y. Shu, A. Simonyi, A. Y. Sun, F. A. Gonzalez, G. A. Weisman, W. G. Wood, G. Y. Sun

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Upregulation and activation of phospholipases A2 (PLA 2) and cyclooxygenases (COX) leading to prostaglandin E 2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1β, TNFα and IFNγ), the P2 nucleotide receptor agonist ATP, and oxidants (H 2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)437-448
Number of pages12
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume69
Issue number6
DOIs
StatePublished - Dec 2003

Bibliographical note

Funding Information:
This work was supported by DHHS grants AA06661, P20 RR15565, P01 AG18357 and P01 ES10535, grant from the Missouri Alzheimer's Disease and Related Disorders Program, and the University of Missouri Food for the 21st Century Program.

Keywords

  • ATP
  • Arachidonic acid
  • Cyclooxygenases
  • Cytokines
  • H O
  • Nitric oxide
  • Phorbol myristate acetate
  • Phospholipases A
  • Prostaglandin E

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