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Purification and characterization of a cyclooxygenase‐2 and angiogenesis suppressing factor produced by human fibroblasts
Author(s) -
Deng WuGuo,
Saunders Michael A.,
Gilroy Derek W.,
He XueZhong,
Yeh Howard,
Zhu Ying,
Shtivelband Mikhail I.,
Ruan KeHe,
Wu Kenneth K.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0844fje
Subject(s) - angiogenesis , carcinogenesis , tumor necrosis factor alpha , cyclooxygenase , cancer research , inflammation , transcription factor , biology , endothelial stem cell , microbiology and biotechnology , cell culture , chemistry , immunology , enzyme , biochemistry , in vitro , gene , genetics
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 12myristate 13‐acetate, interleukin‐1β, tumor necrosis factor α, 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.