Characterization of a cyclooxygenase-2-765G→C promoter polymorphism in human neural cells

Jian Guo Cui, Shabnam Salehi-Rad, Ekaterina Rogaeva, Walter J. Lukiw

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Direct sequencing of the human cyclooxygenase-2 gene promoter revealed a common single nucleotide substitution, cyclooxygenase-2-765G→C, in 24.5% of the populations analyzed. This change introduced a 20 base pair polypyrimidine/polypurine element and a partial recognition feature for RXRα, the 9-cis retinoic acid receptor, into the polymorphic promoter. Cyclooxygenase-2-765G→C constructs, when transfected into human neural cells, exhibited a 1.4-fold higher level of basal expression, while the proinflammatory factors interleukin-1β and 9-cis retinoic acid synergistically induced polymorphic promoter activity 2.4-fold over wild type. These results suggest that under specific conditions of cellular stress, a common variation in cyclooxygenase-2 promoter structure may enhance cyclooxygenase-2 transcription, and this may contribute to the proliferation of an inflammatory response in brain cells.

Original languageEnglish (US)
Pages (from-to)575-579
Number of pages5
JournalNeuroreport
Volume16
Issue number6
DOIs
StatePublished - Apr 25 2005

Keywords

  • 9 cis-retinoic acid
  • Alzheimer's disease
  • Cyclooxygenase-2
  • Inflammatory response
  • Interleukin-1β
  • Neural cells
  • Promoter polymorphism

ASJC Scopus subject areas

  • Neuroscience(all)

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