β-Endorphin stimulates cytokeratin 16 expression and downregulates μ- opiate receptor expression in human epidermis

It has been reported that opioid peptides modulate the differentiation of normal human keratinocytes and that μ-opiate receptors are expressed in human epidermis. The regulation of keratinocyte differentiation is particularly important in psoriasis, and one of the markers for hyperproliferative and differentiating skin diseases is cytokeratin 16. The finding that the endogenous μ-opiate receptor ligand β-endorphin is increased in serum of patients with psoriasis indicates that the μ-opiate system may play an important role in the pathophysiology of the skin. In this study, we addressed the question whether there is a link between μ-opiate receptor regulation and cytokeratin 16 expression in normal and psoriatic skin. Firstly, we demonstrate that β-endorphin concentrations between 16 and 1000 nM significantly downregulate μ-opiate receptor expression in epidermis of cultured human skin after 48h. Secondly, we show that β-endorphin regulates cytokeratin 16 expression in the epidermis of skin organ cultures exposed to 41-125nM β-endorphin for 48h, leading to elevated cytokeratin 16 production. As expected, the expression of cytokeratin 16 was detected primarily in the suprabasal layer. The same pattern was observed in psoriatic lesional skin, i.e., μ-opiate receptor expression was significantly downregulated and cytokeratin 16 expression upregulated. These results suggest that the μ-opiate receptor system and its ligand β-endorphin are involved in the pathogenesis of psoriasis, especially in terms of differentiation.