Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways Academic Article uri icon

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abstract

  • Significance Nonsteroidal antiinflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase-2 (COX-2) induced at sites of inflammation. They are among the most widely used drugs worldwide, but their cardiovascular side effects are a major concern for patients, regulators, and industry. NSAID side effects are mediated by inhibition of constitutively expressed COX-2 present in discrete regions, including the kidney. However, the pathways driving constitutive COX-2 remain poorly understood. The work presented here defines these pathways and importantly shows constitutive COX-2 expression in the kidney occurs through pathways distinct to those driving COX-2 in inflammation. These data therefore highlight the potential that targeting COX-2 at the transcriptional level may provide a way to dissociate antiinflammatory benefits of NSAIDs from their treatment-limiting cardiovascular side effects.

authors

  • Kirkby, Nicholas S
  • Chan, Melissa V
  • Zaiss, Anne K
  • Garcia-Vaz, Eliana
  • Jiao, Jing
  • Berglund, Lisa M
  • Verdu, Elena
  • Ahmetaj-Shala, Blerina
  • Wallace, John L
  • Herschman, Harvey R
  • Gomez, Maria F
  • Mitchell, Jane A

publication date

  • January 12, 2016