Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy
Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy
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DOI：
10.1111/j.1365-2133.2006.07743.x
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发表时间：
2007-05-01
影响因子：
10.3
通讯作者：
Diamandis, E. P.
中科院分区：
文献类型：
--
作者：
Komatsu, N.;Saijoh, K.;Diamandis, E. P.
人组织钾化酶（KLKs）是一个由15个胰蛋白酶样或凝乳胰蛋白酶样分泌丝氨酸蛋白酶（KLK1-KLK15）组成的家族。在正常角质层（SC）和汗液中定量鉴定出多种klk作为候选脱屑相关蛋白酶。目的量化银屑病患者SC和血清中KLK5、KLK6、KLK7、KLK8、KLK10、KLK11、KLK13和KLK14的含量，以及它们在病变区和非病变区、表型、治疗和严重程度之间的差异。测定了SC丝氨酸蛋白酶的总体活性。方法采用酶联免疫吸附法和酶法。结果银屑病皮损SC中所有KLKs含量普遍较高。KLK6、KLK10和KLK13水平在非病变SC中也显著升高，在病变SC中，胰蛋白酶样蛋白、纤溶蛋白样蛋白和furin样蛋白活性均显著升高，在非病变SC中，纤溶蛋白样蛋白活性也显著升高，而在银屑病SC中，促凝胰蛋白酶样蛋白活性仅轻微升高。血清中KLK7水平在正常志愿者和牛皮癣患者之间没有差异。未治疗银屑病患者血清KLK6、KLK8、KLK10和KLK13水平与银屑病面积和严重程度指数评分显著相关。治疗后的银屑病患者血清KLK5和KLK11水平下降，尤其是服用依维甲酸的患者。红皮病型银屑病患者血清KLK水平明显高于正常人、寻常型银屑病或关节病型银屑病患者。结论我们发现银屑病患者SC和血清中KLK水平异常，提示KLK可能参与银屑病的发病机制。
Background Human tissue kallikreins (KLKs) are a family of 15 trypsin-like or chymotrypsin-like secreted serine proteases (KLK1-KLK15). Multiple KLKs have been quantitatively identified in normal stratum corneum (SC) and sweat as candidate desquamation-related proteases.Objectives To quantify KLK5, KLK6, KLK7, KLK8, KLK10, KLK11, KLK13 and KLK14 in the SC and serum of patients with psoriasis, and their variation between lesional and nonlesional areas and with phenotype, therapy and severity. The overall SC serine protease activities were also measured.Methods Enzyme-linked immunosorbent assays and enzymatic assays were used.Results The lesional SC of psoriasis generally contained significantly higher levels of all KLKs. KLK6, KLK10 and KLK13 levels were significantly elevated even in the nonlesional SC. The overall trypsin-like, plasmin-like and furin-like activities were significantly elevated in the lesional SC. Plasmin-like activity was significantly elevated also in the nonlesional SC. The SC chymotrypsin-like activity was only slightly elevated in psoriasis. KLK7 serum levels did not differ between normal volunteers and patients with psoriasis. Serum KLK6, KLK8, KLK10 and KLK13 levels in patients with untreated psoriasis significantly correlated with Psoriasis Area and Severity Index score. Serum KLK5 and KLK11 levels decreased in patients with psoriasis after therapy, especially with etretinate. Patients with erythrodermic psoriasis exhibited significantly higher serum KLK levels than normal subjects or patients with psoriasis vulgaris or arthropathic psoriasis.Conclusions We found aberrant KLK levels in the SC and serum of patients with psoriasis and suggest that KLKs might be involved in the pathogenesis of this disease.