Transgenic mice over-expressing a serine protease in the skin: evidence of interferon gamma-independent MHC II expression by epidermal keratinocytes.
Stratum corneum chymotryptic enzyme (SCCE; also known as kallikrein 7) is a serine protease that is preferentially expressed in cornifying epithelia and possibly involved in the desquamation process. We have recently described transgenic mice over-expressing human SCCE in the epidermis showing increased epidermal thickness, hyperkeratosis, and an apparent dermal inflammation with pruritus. This suggests that SCCE may be involved in the pathophysiology of inflammatory skin diseases. We therefore carried out a further characterization of the skin changes observed in scce-transgenic mice. An increase in number of dermal cells was verified by stereological measurements showing a more than twofold increase of the volume fraction of dermis occupied by cell nuclei. In some, but not all, animals the number of dermal mast cells was increased. The dermal cell infiltrate was shown to consist mainly of macrophages and granulocytes. The number of epidermal and dermal T-lymphocytes was not increased. Dermal changes were found in transgenic animals before the age they became pruritic. No increase in interferon-gamma expression could be detected in the skin of transgenic animals. In spite of this, keratinocytes of adult transgenic mice were found to express MHC II antigen. We suggest that increased expression and/or activity of epidermal SCCE may lead to skin changes that contribute to development and maintenance of inflammatory skin diseases.
Ny
Annelii
A
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Egelrud
Torbjörn
T
D000818:Animals; D015870:Gene Expression; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma; D007610:Kallikreins; D015603:Keratinocytes / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
D007371:Interferon-gamma; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases