title: COX-1 inhibition enhances scratching behaviour in NC/Nga mice with atopic dermatitis.
abstract: NC/Nga (NC) mice, spontaneously develop an eczematous atopic dermatitis (AD)-like skin lesion when kept under conventional condition (Conv), but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model of AD. We have previously shown that PGD(2) and arachidonic acid inhibited the scratching behaviour of NC mice, while indomethacin enhanced it. This study was designed to assess the role of cyclooxygenase (COX)-1 and COX-2 in the itch-related scratching behaviour of NC mice. We examined the expression of COX in the skin using real-time PCR and Western blotting and the effects of SC-560 (a COX-1 selective inhibitor) or NS-398 (a COX-2 selective inhibitor) on scratching behaviour in relation to skin prostaglandin (PG) levels in NC mice. COX-1 mRNA expression was unchanged and protein expression decreased in Conv NC mice compared with that of SPF mice. By contrast, COX-2 mRNA and protein expression increased in Conv NC mice. SC-560 increased scratching behaviour and significantly reduced skin PGD(2), PGE(2) and PGF(2alpha) levels, but NS-398 did not have effects on scratching and skin PG level. Moreover, the topical application of PGD(2), which might be the endogenous inhibitor of itching, suppressed the SC-560-induced enhancement of scratching behaviour by NC mice. These results suggest COX-1-coupled skin PGD(2) biosynthesis plays a physiological role in inhibiting regulation of pruritus in NC mice with AD.
authors.affiliation: Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, Kita-ku, Saitama, Japan. masanori.sugimoto@po.rd.taisho.co.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Iwao
authors.initials: I
authors.lastname: Arai
authors.forename: Nobuko
authors.initials: N
authors.lastname: Futaki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Honma
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakaike
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D002351:Carrageenan / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004487:Edema / Q000378:metabolism; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011537:Pruritus; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D002351:Carrageenan; D051545:Cyclooxygenase 1; D015230:Prostaglandin D2