title: Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis.
abstract: Identification of tissue-specific mechanisms involved in the pathophysiology of inflammatory skin diseases could offer new possibilities to develop effective therapies with fewer systemic effects. The serine protease stratum corneum chymotryptic enzyme is preferentially expressed in cornifying epithelia. We have previously reported on increased expression of the stratum corneum chymotryptic enzyme in psoriasis. Here is reported an increased epidermal expression of stratum corneum chymotryptic enzyme also found in chronic lesions of atopic dermatitis. Transgenic mice expressing human stratum corneum chymotryptic enzyme in suprabasal epidermal keratinocytes were found to develop pathologic skin changes with increased epidermal thickness, hyperkeratosis, dermal inflammation, and severe pruritus. The results suggest that stratum corneum chymotryptic enzyme may be involved in the pathogenesis of inflammatory skin diseases, and that stratum corneum chymotryptic enzyme and related enzymes should be evaluated as potential targets for new therapies.
authors.affiliation: Molecular Biology, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hansson
authors.forename: Assar
authors.initials: A
authors.lastname: Bäckman
authors.forename: Annelii
authors.initials: A
authors.lastname: Ny
authors.forename: Michael
authors.initials: M
authors.lastname: Edlund
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ekholm
authors.forename: Barbro
authors.initials: B
authors.lastname: Ekstrand Hammarström
authors.forename: Jan
authors.initials: J
authors.lastname: Törnell
authors.forename: Pia
authors.initials: P
authors.lastname: Wallbrandt
authors.forename: Håkan
authors.initials: H
authors.lastname: Wennbo
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Egelrud
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D003872:Dermatitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D003876:Dermatitis, Atopic / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000201:enzymology*; D006801:Humans; D007610:Kallikreins; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010641:Phenotype; D011537:Pruritus; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000473:pathology
chemical_list: C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases