Serine proteinase dysfunction in keratinocyte of Papillon-Lefevre syndrome

乳头状瘤综合征（PLS）的特征是掌跖角化病（PPK）和早发性牙周炎，由激活多种丝氨酸蛋白酶的组织蛋白酶C（CTSC）缺乏引起。PPK在PLS中的发病机制尚未确定。我们证实，CTSC激活激肽释放酶8（KLK 8）在永生人类角质形成细胞系; HaCaT细胞，通过刺激重组CTSC。KLK 8是一种丝氨酸蛋白酶，在角质形成细胞的脱落过程中起重要作用。此外，组织病理学发现显示，与野生型相比，局部TPA应用在CTSC敲除小鼠的表皮中引起显著的角化过度。这些发现表明CTSC的缺乏导致丝氨酸蛋白酶功能障碍，导致表皮角化过度。

Papillon-Lefevre syndrome (PLS) is characterized by palmoplantar keratosis (PPK) and early-onset periodontitis, caused by deficiency of cathepsin C (CTSC) that activates many serine proteinases. The pathogenesis of PPK in PLS has not been determined. We confirmed that CTSC activates Kallikrein 8 (KLK8) in immortal human keratinocyte line ; HaCaT cell, by stimulating with recombinant CTSC. KLK8 is one of serine proteinase, and has been reported that plays a role in shedding the corneocytes. Furthermore, histopathological finding showed that topical TPA application caused significant hyperkeratosis in the epidermis of CTSC knockout mice, compared to wild type. These findings suggest that an absence of CTSC causes a serine proteinase dysfunction, leads to hyperkeratosis in the epidermi.