The activity of caspase-1 is increased in lesional psoriatic epidermis
The activity of caspase-1 is increased in lesional psoriatic epidermis
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DOI：
10.1038/sj.jid.5700922
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发表时间：
2007-12-01
影响因子：
6.5
通讯作者：
Iversen, Lars
中科院分区：
文献类型：
--
作者：
Johansen, Claus;Moeller, Kristine;Iversen, Lars
半胱天冬酶-1属于炎性半胱天冬酶组，是促炎细胞因子IL-18的活化酶，IL-18是已知在银屑病发病机制中起重要作用的细胞因子。本研究的目的是确定caspase-1在银屑病皮肤中的表达以及参与应激诱导caspase-1和IL-18活化的信号机制。有趣的是，与非皮损性银屑病皮肤相比，皮损中的caspase-1活性增加。在体外培养的人角质形成细胞的实验表明，茴香霉素诱导的，p38丝裂原活化蛋白激酶（p38 MAPK）依赖性增加的半胱天冬酶原-1和活性半胱天冬酶-1的分泌。此外，茴香霉素通过p38 MAPK依赖性但caspase-1非依赖性机制增加IL-18的mRNA表达，在刺激12小时后达到最大水平。最后，茴香霉素引起proIL-18和活性IL-18分泌的快速（4小时）增加。活性IL-18的分泌通过p38 MAPK/caspase-1依赖性机制介导，而proIL-18的分泌通过p38 MAPK依赖性但caspase-1非依赖性机制介导。这些数据表明，银屑病皮肤中caspase-1的活性增加，IL-18的分泌受p38 MAPK/caspase-1依赖性机制的调节，使caspase-1成为银屑病治疗的潜在靶点。
Caspase-1 belongs to the group of inflammatory caspases and is the activating enzyme for the proinflammatory cytokine IL-18, a cytokine known to play an important role in the pathogenesis of psoriasis. The purpose of this study was to determine the expression of caspase-1 in psoriatic skin and the signaling mechanisms involved in stress-induced activation of caspase-1 and IL-18. Interestingly, increased caspase-1 activity in lesional compared with non-lesional psoriatic skin was seen. In vitro experiments in cultured human keratinocytes demonstrated anisomycin-induced, p38 mitogen-activated protein kinase (p38 MAPK)-dependent increased secretion of procaspase-1 and active caspase-1. Furthermore, anisomycin increased the mRNA expression of IL-18 through a p38 MAPK-dependent but caspase-1-independent mechanism, reaching a maximum level after 12 hours of stimulation. Finally, anisomycin caused a rapid (4 hours) increase in the secretion of proIL-18 and active IL-18. Secretion of active IL-18 was mediated through a p38 MAPK/caspase-1-dependent mechanism, whereas secretion of proIL-18 was mediated by a p38 MAPK-dependent but caspase-1-independent mechanism. These data demonstrate that the activity of caspase-1 is increased in psoriatic skin and that IL-18 secretion is regulated by a p38 MAPK/caspase-1-dependent mechanism, making caspase-1 a potential target in the treatment of psoriasis.