Reference - Detail
| RRC ID | 41542 |
|---|---|
| Author | Hirose M, Miwa H, Kobayashi O, Oshida K, Misawa H, Kurosawa A, Watanabe S, Sato N. |
| Title | Inhibition of proliferation of gastric epithelial cells by a cyclooxygenase 2 inhibitor, JTE522, is also mediated by a PGE2-independent pathway. |
| Journal | Aliment Pharmacol Ther |
| Abstract |
BACKGROUND:Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes for prostaglandin synthesis from arachidonic acid. Although it is known that inhibition of cyclooxygenase activity delays ulcer healing, the regulatory relationship between COX-2 and its metabolites in gastric epithelial cell proliferation is not well known. AIM:To investigate whether COX-2 has an effect on gastric mucosal cell proliferation and further studied whether such effect is mediated only by prostaglandin E2 (PGE2), a representative metabolite of arachidonates in the gastric mucosa. METHODS:Artificial wounds of defined area size were created on complete monolayer cell sheets of isolated rat gastric epithelial cells and rat gastric cell line RGM1 under the addition of arachidonic acid or a COX-2 selective inhibitor, JTE522. Repair of wounds was assessed by monitoring wound size, with cell proliferation detected using 5-bromodeoxyuridine staining. Quantity of secreted PGE2 was measured by enzyme immunoassay. RESULTS:Stimulation of foetal calf serum increased the expression of COX-2 protein and inhibition of COX-2 retarded wound healing with reduction of cell proliferation. Arachidonic acid increased PGE2 production and accelerated restoration. Combination of JTE522 and arachidonic acid resulted in a marked retardation of wound healing compared to the control, but JTE522 did not completely suppress the increase in cellular PGE2 content following the addition of arachidonate. CONCLUSIONS:The difference in the effects of JTE522 on PGE2 production and on wound healing suggest that the involvement of COX-2 in gastric epithelial cell proliferation is not mediated solely by PGE2. |
| Volume | 16 Suppl 2 |
| Pages | 83-9 |
| Published | 2002-4-1 |
| DOI | 10.1046/j.1365-2036.16.s2.28.x |
| PII | 156 |
| PMID | 11966528 |
| MeSH | Animals Arachidonic Acid / pharmacology Benzenesulfonates / pharmacology* Cell Division / drug effects Cell Line Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology* Dinoprostone / biosynthesis* Epithelial Cells / cytology Epithelial Cells / drug effects Gastric Mucosa / cytology* Gastric Mucosa / drug effects Isoenzymes / antagonists & inhibitors* Isoenzymes / metabolism Male Oxazoles / pharmacology* Prostaglandin-Endoperoxide Synthases / metabolism Rats Rats, Wistar Wound Healing / drug effects |
| IF | 7.515 |
| Times Cited | 10 |
| WOS Category | GASTROENTEROLOGY & HEPATOLOGY PHARMACOLOGY & PHARMACY |
| Resource | |
| Human and Animal Cells | RGM1(RCB0876) |