Helicobacter pylori induces cyclooxygenase-1 and cyclooxygenase-2 expression in vascular endothelial cells.
BACKGROUND
Helicobacter pylori induces cyclooxygenase activity in the stomach, although the COX isoform and cellular source are unclear. A potential source is the vascular endothelial cell, which plays a role in regulating mucosal blood flow and inflammatory cell infiltration.


METHODS
We examined the effect of four strains (toxigenic and non-toxigenic) of H. pylori on COX isoform expression in vascular endothelial cells. Prostaglandin synthesis was measured by enzyme immunoassay and COX isozyme expression determined by Western blot and RT-PCR. Gene induction was examined using 5' deletion constructs of the COX-1 and COX-2 promoters coupled with luciferase.


RESULTS
All H. pylori strains induced prostaglandin generation and expression of both COX-1 and COX-2 in HUVEC, although this was most pronounced with the highly toxigenic strain H. pylori 60190. Treatment of the cells with selective COX inhibitors demonstrated that COX-1 was predominantly responsible for the enhanced generation of prostacyclin induced by H. pylori 60190. Similar results were seen with H. pylori broth culture filtrates, suggesting that a secreted product was responsible. Induction of COX-2 reflected both enhanced gene expression and stabilization of the mRNA.


CONCLUSIONS
H. pylori increased both COX-1 and COX-2 activity in vascular endothelial cells. This increased generation of endothelial cell prostacyclin may play a role in modulating mucosal blood flow, platelet function and inflammatory cell infiltration in response to H. pylori infection. The regulation of COX-1 at the transcriptional level by H. pylori described in this study is a novel finding and calls into question the traditional description of COX-1 as a purely constitutive, housekeeping gene.
Byrne
M F
MF
Dept. of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland. mfbyrne@rcsi.ie
Murphy
J F
JF
Corcoran
P A
PA
Atherton
J C
JC
Sheehan
K M
KM
Cox
D
D
Murray
F E
FE
Fitzgerald
D J
DJ
D015153:Blotting, Western; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D042783:Endothelial Cells / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D008565:Membrane Proteins; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases