Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats.
It has been reported that cyclooxygenase-2 (COX-2) may play a crucial role in gastric ulcer healing. We examined the localization of COX-2 and the regulation of COX-2 mRNA expression in acetic acid ulcers in rats. PGE2 production was elevated in ulcerated tissue but not in intact tissue. COX-2 mRNA expression was induced in only the ulcerated tissue, and COX-2 protein was found in fibroblasts, monocytes/macrophages, and granulocytes. A selective COX-2 inhibitor inhibited increased PGE2 production by the ulcerated tissue. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) mRNAs were also expressed only in the ulcerated tissue. In a culture of isolated ulcer base, blockade of IL-1beta and TNF-alpha reduced COX-2 mRNA expression and PGE2 production. In contrast, COX-2 mRNA expression and PGE2 production were promoted by prevention of TGF-beta1 action. These results indicate that COX-2 protein is highly localized in the base of gastric ulcers in rats and that COX-2 mRNA expression might be regulated positively by IL-1beta and TNF-alpha and negatively by TGF-beta1.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Shigeta
J
J
Inoue
H
H
Tanabe
T
T
Okabe
S
S
D019342:Acetic Acid; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012016:Reference Values; D013276:Stomach Ulcer / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D000906:Antibodies; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D019342:Acetic Acid