Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in mice.
We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.
Sugimoto
M
M
Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Kita-ku, Saitama 331-9530, Japan. masanori.sugimoto@po.rd.taisho.co.jp
Arai
I
I
Futaki
N
N
Hashimoto
Y
Y
Honma
Y
Y
Nakaike
S
S
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000096:biosynthesis; D051379:Mice; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011537:Pruritus / Q000473:pathology; D012867:Skin / Q000201:enzymology / Q000293:injuries* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D011453:Prostaglandins; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001241:Aspirin; D015230:Prostaglandin D2