title: Immediate-type allergic and protease-mediated reactions are involved in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice.
abstract: Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behaviour after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behaviour in each phase. An increase in the content of mast cell-derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application. Chlorpheniramine (H1receptor antagonist) and cromoglycate (mast cell stabilizer) reduced the scratching behaviour in the early phase but not that in the later phase. Furthermore, the content of various endogenous pruritogens such as interleukin-31 and thymic stromal lymphopoietin in the lesional skin was increased 1 or 24 hours after the Dfb ointment application. Elevated expression of proteinase-activated receptor-2 (PAR-2) was also observed in the epidermis. Finally, gabexate (serine protease inhibitor) reduced the scratching behaviour in both phases, and anti-PAR2 antibody also showed a tendency to reduce both scratching behaviours. These findings suggest that immediate-type allergic reactions caused by mast cell degranulation and PAR-2 activation by proteases are involved in the scratching behaviour in this AD-like model.
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Yoshihito
authors.identifier: 0000-0003-4370-7594
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kanayama
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Tamura
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Strategic Research Planning & Management Department, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000982:Antipruritics / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002744:Chlorpheniramine / Q000627:therapeutic use; D045424:Complex Mixtures; D004205:Cromolyn Sodium / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D040001:Dermatophagoides farinae; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism; D005260:Female; D016670:Gabexate / Q000627:therapeutic use; D006632:Histamine / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007155:Immunologic Factors / Q000627:therapeutic use; D007378:Interleukins / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D009824:Ointments; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000276:immunology / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000906:Antibodies; D000982:Antipruritics; D045424:Complex Mixtures; D016207:Cytokines; C000628463:F2rl1 protein, mouse; D007155:Immunologic Factors; D007378:Interleukins; D009824:Ointments; D044464:Receptor, PAR-2; D015842:Serine Proteinase Inhibitors; C502588:interleukin-31, mouse; D012701:Serotonin; D002744:Chlorpheniramine; D016670:Gabexate; D006632:Histamine; D004205:Cromolyn Sodium; D000094632:Thymic Stromal Lymphopoietin
keywords: atopic dermatitis; house dust mites; protease; pruritogen