Department of Pharmacy, University of Patras, Greece.
Biol Chem. 2010 Apr;391(4):321-31. doi: 10.1515/BC.2010.036.
Kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases encoded by the largest uninterrupted cluster of protease-encoding genes within the human genome. Recent studies, mostly relying on in vitro proteolysis of recombinant proteins, have suggested that KLK activities are regulated by proteolytic activation cascades that can operate in a tissue-specific manner, such as the semen liquefaction and skin desquamation cascades. The validity of KLK activation cascades in vivo largely remains to be demonstrated. Here, we focus on recent investigations showing that KLKs represent interesting players in the broader field of immunology based on their ability to bridge their inherent ability to degrade the extracellular matrix with major functions of the immune system. More specifically, KLKs assist in the infiltration of immune cells through the skin and the blood brain barrier, whereas they catalyze the generation of antimicrobial peptides by proteolytic activation and further processing of protein precursors. In an attempt to integrate current knowledge, we propose KLK-mediated pathways that are putatively involved in inflammation associated with skin wounding and central nervous system disorders, including multiple sclerosis. Finally, we present evidence of KLK participation in autoimmune diseases and allergies.
激肽释放酶相关肽酶（KLKs）构成了一个由 15 种高度保守的丝氨酸蛋白酶组成的家族，这些蛋白酶由人类基因组中最大的连续蛋白酶编码基因簇编码。最近的研究，主要依赖于重组蛋白的体外蛋白水解，表明 KLK 活性受到蛋白水解激活级联的调节，这种级联可以以组织特异性的方式发挥作用，如精液液化和皮肤脱屑级联。KLK 激活级联在体内的有效性在很大程度上仍有待证明。在这里，我们关注的是最近的研究结果，这些研究结果表明 KLKs 基于其将固有降解细胞外基质的能力与免疫系统的主要功能联系起来的能力，代表了免疫学这一更广泛领域的有趣参与者。更具体地说，KLKs 有助于免疫细胞通过皮肤和血脑屏障的渗透，同时通过蛋白水解激活和蛋白前体的进一步加工，催化抗菌肽的生成。为了整合当前的知识，我们提出了 KLK 介导的途径，这些途径可能与皮肤创伤和中枢神经系统疾病（包括多发性硬化症）相关的炎症有关。最后，我们提出了 KLK 参与自身免疫性疾病和过敏的证据。
