Purification and characterization of a cyclooxygenase-2 and angiogenesis suppressing factor produced by human fibroblasts

FASEB J. 2002 Aug;16(10):1286-8. doi: 10.1096/fj.01-0844fje. Epub 2002 Jun 7.


Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays an important role in several pathophysiological processes, including inflammation, angiogenesis, and tumorigenesis. We have recently observed that COX-2 induction is restrained in proliferating fibroblasts. The mechanism by which this occurs is unclear. Here, we report the detection and isolation from the conditioned medium of proliferating fibroblasts a factor that suppressed COX-2 expression. This factor, which was named cytoguardin, suppressed COX-2 protein levels induced by phorbol 12-myristate 13-acetate, interleukin-1beta, tumor necrosis factor alpha, and lipopolysaccharide (LPS) in fibroblasts and LPS-induced COX-2 protein levels and promoter activities in human endothelial cells and murine RAW 264.7 cells in a comparable concentration-dependent manner. It inhibited COX-2 expression induced by angiogenic factors and endothelial tube formation induced by angiogenic factors and colon cancer cell medium. These findings provide evidence for the control of COX-2 transcription by an endogenous cellular factor.

MeSH terms

  • Angiogenesis Inhibitors / isolation & purification*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Colonic Neoplasms / chemistry
  • Culture Media, Conditioned / chemistry
  • Cyclooxygenase 2
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / growth & development
  • Fibroblasts / chemistry*
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Gene Expression Regulation
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Mice
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Angiogenesis Inhibitors
  • Culture Media, Conditioned
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases