Enkephalins modulate differentiation of normal human keratinocytes in vitro

• Published in: Experimental dermatology 1997-10, Vol.6 (5), p.222-229
• Main Authors: Nissen, Judith B., Kragballe, Knud
• Format: Article
• Language: English
• Subjects: beta-Endorphin - pharmacology; Cell Differentiation - drug effects; Cell Division - drug effects; Cells, Cultured; differentiation; Dose-Response Relationship, Drug; endorphin; enkephalin; Enkephalin, Leucine - antagonists & inhibitors; Enkephalin, Leucine - pharmacology; Enkephalin, Leucine-2-Alanine - analogs & derivatives; Enkephalin, Leucine-2-Alanine - pharmacology; Enkephalin, Methionine - antagonists & inhibitors; Enkephalin, Methionine - pharmacology; Humans; keratinocyte; Keratinocytes - cytology; Keratinocytes - drug effects; Keratins - metabolism; Melphalan - analogs & derivatives; Melphalan - pharmacology; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; proliferation; Skin - cytology; Skin - drug effects; Transglutaminases - metabolism
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.1997.tb00166.x

Opioid peptides are a group of neuropeptides which include enkephalins, endorphins and dynorphins. In addition to their central and peripheral antinociceptive function, opioids can modulate immune activity and cell proliferation. Previously, we have shown that enkephalins are present in macrophages infiltrating the dermal papillae in involved psoriatic skin and that the amount of enkephalin is significantly increased in involved psoriatic skin. Because enkephalins were detected close to the epidermis, we examined the effects of opioid peptides on the differentiation (transglutaminase type 1 activity and cytokeratin 10 expression) and proliferation (MTT assay) of cultured human keratinocytes. Enkephalins (methionine‐enkephalin, leucine‐cnkephalin and the synthetic DADL) inhibited cell differentiation dose‐dependently, while β‐endorphin had no effect. The opioid receptor antagonist naltrexone completely antagonized the inhibitory effect of methionine‐enkephalin and leucine‐enkephalin. but not that of DADL. Furthermore, methionine‐enkephalin had a slight inhibitory effect on the proliferation of keralinocytcs. Enkephalin was detected in unstimulated keratinocyte cultures, and naltrexone alone stimulated keratinocyte differentiation. These results indicate that enkephalins may play a role in the differentiation of epidermal keratinocytes. It remains to be determined whether the enkephalin detected in psoriatic skin are sufficient to affect epidermal differentiation in vivo.