Tumor necrosis factor α and interleukin-1β stimulate the expression of cyclooxygenase II but do not alter prostaglandin E 2 receptor mRNA levels in cultured dorsal root ganglia cells

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Abstract

Tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are pro-inflammatory cytokines capable of altering the sensitivity of sensory neurons. Because sensitization elicited by IL-1β and TNFα is blocked by inhibition of the inducible enzyme, cyclooxygenase-II (COX-2), we examined whether these cytokines could increase COX-2 expression in dorsal root ganglion (DRG) cultures. Treatment of cell cultures with either IL-1β or TNFα increases immunoreactive COX-2, as measured by immunoblotting, in a time- and concentration-dependent manner. A 24-h pretreatment with 10 ng/ml IL-1β or 50 ng/ml TNFα augmented COX-2 expression 50- and 8-fold over basal levels, respectively. Immunohistochemistry established the presence of COX-2-like immunoreactivity in both neuronal and non-neuronal cells in culture. The addition of IL-1 receptor antagonist blocked the induction of COX-2 expression by IL-1β, but did not alter TNFα-stimulated increases in COX-2, indicating that the mechanism of TNFα is not limited to increasing the expression of IL-1β. The basal and TNFα-induced expression of COX-2 was not dependent on the presence of NGF in the growth media. IL-1β and TNFα treatment for 24 h enhanced prostaglandin E 2 (PGE 2) production 2-4-fold, which was blocked by pretreatment with the COX-2 inhibitor, NS-398. Exposing cultures to PGE 2, IL-1β, or TNFα for 24 h did not alter PGE 2 receptor (EP) mRNA levels. These results indicate that TNFα and IL-1β induce the functional expression of COX-2 but not EP receptors in DRG cells in culture and suggest that cytokine-induced sensitization of sensory neurons is secondary to prostaglandin production and not alterations in EP receptors.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalPain
Volume113
Issue number1-2
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Cyclooxygenase
  • Cytokine
  • Dorsal root ganglia
  • Prostaglandin E
  • Prostaglandin receptor
  • Sensory neuron

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

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