Signalling networks regulating cyclooxygenase-2

Int J Biochem Cell Biol. 2006;38(10):1654-61. doi: 10.1016/j.biocel.2006.03.021. Epub 2006 Apr 25.


Cyclooxygenease-2 (COX-2) is the key enzyme regulating the production of prostaglandins, central mediators of inflammation. The expression of cyclooxygenease-2 is induced by several extra cellular signals including pro-inflammatory and growth-promoting stimuli. All signals converge to the activation of mitogen-activated protein kinases (MAPK) that regulate cyclooxygenease-2 mRNA levels both at the transcriptional and post-transcriptional level. The machinery appears to be highly specialized involving activation of distinct signalling molecules depending on the type of extracellular stimulus. Expression of cyclooxygenease-2 mRNA is regulated by several transcription factors including the cyclic-AMP response element binding protein (CREB), nuclear factor kappa B (NFkB) and the CCAAT-enhancer binding protein (C/EBP). Cyclooxygenease-2 is also affected post-transcriptionaly, at the level of mRNA stability. Finally, cyclooxygenease-2 can be affected directly at its enzymatic activity by nitric oxide and nitric oxide synthase (iNOS). Each step of cyclooxygenease-2 regulation can be used as potential therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / physiology*
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Mice
  • Prostaglandins / metabolism
  • Signal Transduction


  • Cyclooxygenase 2 Inhibitors
  • Prostaglandins
  • Cyclooxygenase 2