Hansson Lennart, Bäckman Assar, Ny Annelii, Edlund Michael, Ekholm Elisabeth, Ekstrand Hammarström Barbro, Törnell Jan, Wallbrandt Pia, Wennbo Håkan, Egelrud Torbjörn
Molecular Biology, AstraZeneca R&D, Mölndal, Sweden.
J Invest Dermatol. 2002 Mar;118(3):444-9. doi: 10.1046/j.0022-202x.2001.01684.x.
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.
识别炎症性皮肤病病理生理学中涉及的组织特异性机制,可能为开发具有较少全身作用的有效疗法提供新的可能性。丝氨酸蛋白酶角质层糜蛋白酶样酶在角质形成上皮中优先表达。我们之前报道过银屑病中角质层糜蛋白酶样酶的表达增加。本文报道在特应性皮炎的慢性皮损中也发现角质层糜蛋白酶样酶的表皮表达增加。在基底上层表皮角质形成细胞中表达人角质层糜蛋白酶样酶的转基因小鼠出现了病理性皮肤变化,表现为表皮厚度增加、角化过度、真皮炎症和严重瘙痒。结果表明,角质层糜蛋白酶样酶可能参与炎症性皮肤病的发病机制,角质层糜蛋白酶样酶及相关酶应作为新疗法的潜在靶点进行评估。