Interleukin-1β induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures

M. Kerry O'Banion, Janice C. Miller, Julia W. Chang, Mitchell D. Kaplan, Paul Coleman

Research output: Contribution to journalArticle

189 Scopus citations

Abstract

Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS- 2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production of prostaglandin E2 (PGE2) after stimulation with either interleukin-1β (IL-1β) or the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). This increase in PGE2 content was blocked by pretreatment with dexamethasone and correlated with increases in cyclooxygenase activity measured at 4 h. Northern blots revealed concomitant increases in PGHS-2 mRNA levels that peaked at 2 h and were dependent on the dosage of IL-1β. Dexamethasone inhibited this induction of PGHS-2 mRNA by IL-1β. TPA, basic fibroblast growth factor, and the proinflammatory factors tumor necrosis factor α and lipopolysaccharide, but not interleukin-6, also stimulated PGHS-2 mRNA expression. Relative to IL-1β, the greater increases in PGE2 production and cyclooxygenase activity caused by TPA correlated with a greater induction of PGHS-2 mRNA. Furthermore, NS-398, a specific inhibitor of cyclooxygenase-2, blocked >80% of the cyclooxygenase activity in TPA-treated astrocytes. These findings indicate that increased expression of PGHS-2 contributes to prostaglandin production in cultured astrocytes exposed to cytokines and other factors.

Original languageEnglish (US)
Pages (from-to)2532-2540
Number of pages9
JournalJournal of Neurochemistry
Volume66
Issue number6
StatePublished - Jun 1 1996
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • Brain injury
  • Cytokines
  • Glia
  • Glucocorticoids

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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