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银屑病患者角质层和血清中异常的人组织激肽释放酶水平:取决于表型、严重程度和治疗情况。

Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy.

作者信息

Komatsu N, Saijoh K, Kuk C, Shirasaki F, Takehara K, Diamandis E P

机构信息

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.

出版信息

Br J Dermatol. 2007 May;156(5):875-83. doi: 10.1111/j.1365-2133.2006.07743.x.

Abstract

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.

摘要

背景

人组织激肽释放酶(KLKs)是一个由15种胰蛋白酶样或糜蛋白酶样分泌丝氨酸蛋白酶组成的家族(KLK1-KLK15)。已在正常角质层(SC)和汗液中定量鉴定出多种KLKs,作为与脱屑相关的候选蛋白酶。

目的

定量检测银屑病患者SC和血清中的KLK5、KLK6、KLK7、KLK8、KLK10、KLK11、KLK13和KLK14,以及它们在皮损和非皮损区域之间的差异,及其与表型、治疗和严重程度的关系。还测量了整体SC丝氨酸蛋白酶活性。

方法

采用酶联免疫吸附测定法和酶活性测定法。

结果

银屑病皮损SC中所有KLKs的水平通常显著更高。即使在非皮损SC中,KLK6、KLK10和KLK13的水平也显著升高。皮损SC中整体胰蛋白酶样、纤溶酶样和弗林蛋白酶样活性显著升高。非皮损SC中的纤溶酶样活性也显著升高。银屑病中SC糜蛋白酶样活性仅略有升高。正常志愿者和银屑病患者的血清KLK7水平无差异。未经治疗的银屑病患者血清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。银屑病患者治疗后血清KLK5和KLK11水平下降,尤其是使用依曲替酯治疗后。红皮病型银屑病患者的血清KLK水平显著高于正常受试者、寻常型银屑病患者或关节病型银屑病患者。

结论

我们发现银屑病患者SC和血清中的KLK水平异常,并提示KLKs可能参与了该疾病的发病机制。

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