Faculty of Medicine, Shiga University of Medical Science, Otsu, Japan.
Division of Anatomy and Cell Biology, Shiga University of Medical Science, Otsu, Japan.
J Invest Dermatol. 2015 Mar;135(3):776-785. doi: 10.1038/jid.2014.448. Epub 2014 Oct 14.
Human prolactin-induced protein (PIP) is a major protein found in exocrine fluids such as saliva and sweat. Intriguingly, PIP possesses residues (human PIP (hPIP): PIP (29-63)) that display similarity to the aspartic peptidase candidapepsin. Here, we aimed to determine the effect of PIP as a protease on normal skin structure. Using an adhesive tape-stripping technique, we applied hPIP peptide on the corneocytes of normal-appearing facial skin from infants with eczema and healthy infants and then analyzed the morphological structure of corneocytes with Nile Red fluorescence. We also repeatedly applied the hPIP peptide onto the surface of a three-dimensional (3-D) human skin model and then analyzed any changes to the stratum corneum and epidermis using light microscopy and scanning electron microscopy. In both infant groups, a decrease in hydrophobic lipids from the cornified envelope was observed after treatment with hPIP. The peptide hPIP appeared to digest the fine structure of the stratum corneum and induce a proliferation of epidermal keratinocytes within the 3-D human skin model. Our results suggest that aspartic peptidase of PIP found in sweat or saliva deteriorates the skin barrier in a de novo manner, which potentially leads directly to the proliferation of epidermal keratinocytes without any external antigenic factors.
人催乳素诱导蛋白（PIP）是一种主要存在于外分泌液（如唾液和汗液）中的蛋白质。有趣的是，PIP 含有与天冬氨酸蛋白酶 Candidapepsin 相似的残基（人 PIP（hPIP）：PIP（29-63））。在这里，我们旨在确定 PIP 作为一种蛋白酶对正常皮肤结构的影响。我们使用胶带剥离技术，将 hPIP 肽应用于湿疹婴儿和健康婴儿正常面部皮肤的角朊细胞上，然后用尼罗红荧光分析角朊细胞的形态结构。我们还将 hPIP 肽反复应用于三维（3-D）人体皮肤模型的表面，然后用光显微镜和扫描电子显微镜分析角质层和表皮的任何变化。在两组婴儿中，在用 hPIP 处理后，观察到来自角蛋白包膜的疏水性脂质减少。该肽 hPIP 似乎消化了角质层的精细结构，并在 3-D 人体皮肤模型中诱导表皮角质形成细胞的增殖。我们的结果表明，汗液或唾液中发现的天冬氨酸蛋白酶 PIP 以全新的方式破坏皮肤屏障，这可能直接导致表皮角质形成细胞增殖，而无需任何外部抗原因素。
