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.

Animal eggs are generally encased in one or more extra-cellular coats that protect the egg from biological, chemical and mechanical hazards. These coats contain some essential molecules for sperm to fertilise an appropriate egg, such as the specific ligand for sperm binding and the specific signal for induction of the acrosome reaction. In starfish, the outermost egg coat is a relatively thick gelatinous layer called the jelly coat. When starfish sperm encounter the jelly coat of homologous eggs, they undergo the acrosome reaction within a second or less (Dale et al., 1981; Ikadai & Hoshi, 1981; Sase et al., 1995). We have thus searched the jelly coat for the signal molecule(s) that triggers the acrosome reaction in the starfish, Asterias amurensis. It is known that three components in the jelly coat, namely acrosome reaction-inducing substance (ARIS), Co-ARIS and asterosap, act in concert on homologous spermatozoa to elicit the acrosome reaction immediately and efficiently (Hoshi et al., 1994,1999).ARIS alone induces the acrosome reaction only in high calcium or high pH seawater. In normal seawater, besides ARIS, either Co-ARIS or asterosap is required for the induction. Without ARIS, no combination of Co-ARIS and asterosap can induce the acrosome reaction in normal, high calcium or high pH seawater. A mixture of ARIS and Co-ARIS increases the intracellular Ca2+ level, whereas asterosap increases the intra-cellular pH (Matsui et al., 1986a, b; Nishigaki et al., 1996). These events are prerequisites for the induction of the acrosome reaction. Indeed, the triad of ARIS, CoARIS and asterosap provides the best conditions for the induction of the acrosome reaction in normal sea-water (Hoshi et al., 1994, 1999).