Purification and characterization of a cyclooxygenase-2 and angiogenesis suppressing factor produced by human fibroblasts.
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.
Deng
Wu-Guo
WG
Vascular Biology Research Center, Institute of Molecular Medicine, and Division of Hematology, University of Texas-Houston Medical School, Houston, Texas, USA.
Saunders
Michael  A
M
Gilroy
Derek  W
D
He
Xue-Zhong
XZ
Yeh
Howard
H
Zhu
Ying
Y
Shtivelband
Mikhail I
MI
Ruan
Ke-He
KH
Wu
Kenneth K
KK
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D003110:Colonic Neoplasms / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000737:chemistry; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development; D005347:Fibroblasts / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases