Iversen Lars, Johansen Claus
Department of Dermatology, Aarhus University Hospital, PP Orumsgade 11, DK-8000 Aarhus C, Denmark.
Expert Rev Mol Diagn. 2008 Nov;8(6):697-705. doi: 10.1586/14737159.8.6.697.
The inflammatory caspases comprise a subclass of caspases associated with immune responses. Caspase-1 was the first identified member of this class, which also includes caspase-4, -5, -11 and -12. Caspase-1 was identified as the IL-1beta-converting enzyme and, more recently, it has also been shown to activate IL-18 and IL-33. Activation of the inflammatory caspases occurs upon assembly of multiprotein complexes, termed inflammasomes. The inflammasomes and inflammatory caspases are part of the innate immune system, which constitutes the first line of defense that detects pathogens, such as nonself antigens, bacterial and viral components, and other danger signals, and orchestrates the immune response. Inflammasomes and inflammatory caspases have also been suggested to bridge the innate immune responses to the adaptive immune system. More recently, the expression and role of inflammasomes and inflammatory caspases have been studied in both human and rodent skin, and findings have indicated a possible key role of these regulators of the immune system in the pathogenesis of inflammatory skin diseases. This article will review some of the most recent findings, identifying inflammasomes and inflammatory caspases as potential inducers and regulators of skin inflammation in contact hypersensitivity and psoriasis.
炎症性半胱天冬酶构成了与免疫反应相关的半胱天冬酶亚类。半胱天冬酶 -1是该类中首个被鉴定出的成员,该类还包括半胱天冬酶 -4、-5、-11和 -12。半胱天冬酶 -1被鉴定为白细胞介素 -1β转化酶,最近还发现它能激活白细胞介素 -18和白细胞介素 -33。炎症性半胱天冬酶的激活发生在多蛋白复合物(即炎性小体)组装时。炎性小体和炎症性半胱天冬酶是先天性免疫系统的一部分,先天性免疫系统构成了检测病原体(如非自身抗原、细菌和病毒成分以及其他危险信号)的第一道防线,并协调免疫反应。炎性小体和炎症性半胱天冬酶也被认为是连接先天性免疫反应和适应性免疫系统的桥梁。最近,已经对人类和啮齿动物皮肤中炎性小体和炎症性半胱天冬酶的表达及作用进行了研究,结果表明这些免疫系统调节因子在炎症性皮肤病的发病机制中可能起着关键作用。本文将综述一些最新研究发现,确定炎性小体和炎症性半胱天冬酶是接触性超敏反应和银屑病中皮肤炎症的潜在诱导剂和调节因子。