Expression of cyclooxygenase 1 and 2 by human gastric endothelial cells.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. NSAIDs also impair granulation tissue angiogenesis and healing of established gastric ulcers in humans. The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inhibition of either or both COX isoforms (COX-1 and COX-2).


OBJECTIVE
To investigate COX expression by human gastric endothelial (HuGE) cells during angiogenesis in vitro.


METHODS
COX-1 and COX-2 expression by HuGE cells was investigated by western blot analysis, indirect immunofluorescence, reverse transcriptase polymerase chain reaction, and measurement of prostaglandin E(2) synthesis. Plating onto basement membrane matrix and stimulation by phorbol ester were used as in vitro models of angiogenesis.


RESULTS
Under normal culture conditions (30% serum), HuGE cells expressed COX-1 and low levels of COX-2. COX-2 expression was induced in HuGE cells in both angiogenesis models. Prostaglandin E(2) production and tubular structure formation by HuGE cells on basement membrane matrix was significantly inhibited by a selective COX-2 inhibitor (NS-398).


CONCLUSIONS
Angiogenesis by HuGE cells in vitro was associated with induction of functional COX-2 expression. A selective COX-2 inhibitor significantly decreased HuGE cell angiogenesis on basement membrane matrix. Extrapolation of these data to human gastric ulcer angiogenesis in vivo suggests that selective COX-2 inhibitors could delay gastric ulcer healing to the same extent as traditional NSAIDs which are non-selective COX inhibitors.
Hull
M A
MA
Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham, UK. medmah@stjames.leeds.ac.uk
Thomson
J L
JL
Hawkey
C J
CJ
D015153:Blotting, Western; D018929:Cell Culture Techniques; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000201:enzymology; D005109:Extracellular Matrix; D019084:Fluorescent Antibody Technique, Indirect; D005753:Gastric Mucosa / Q000098:blood supply / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007797:Laminin; D008565:Membrane Proteins; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004338:Drug Combinations; D007527:Isoenzymes; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone