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Maria Gomez

Maria Gomez

Professor

Maria Gomez

Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways.

Author

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

Summary, in English

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system.

Department/s

  • Diabetic Complications
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Vascular Physiology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2016

Language

English

Pages

434-439

Publication/Series

Proceedings of the National Academy of Sciences

Volume

113

Issue

2

Document type

Journal article

Publisher

National Acad Sciences

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Diabetic Complications
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Vascular Physiology

ISBN/ISSN/Other

  • ISSN: 1091-6490