Modulation of endothelin-1 in normal human keratinocytes by UVA1/B radiations, prostaglandin E2 and peptidase inhibitors.
In the skin, keratinocytes synthesize and secrete endothelin-(ET-1), a potent vasoconstrictor peptide which acts also as a growth factor for most skin cells. The aim of the study was to test the effects of UVA1 and the associations UVA1/B on the expression of ET-1 in normal human keratinocytes and to determine whether exogenously added prostaglandin E2 (PGE2) regulated ET-1 expression. As ET-1 is susceptible to degradation, we also evaluated whether ET-1 secretion was modulated by peptidase inhibitors. Our results showed that UVA1 (365 nm) did not modify the levels of preproET-1 mRNA and protein. Moreover, the associations UVA1+UVB or UVB+UVA1 down-regulated the overexpression of secreted ET-1 induced by UVB alone. PGE2 at 10(-5) M reduced the expression of ET-1 at the mRNA and protein levels but did not exert any significant modification at lower concentrations from 10(-10) to 10(6) M. Phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, drastically decreased the amount of ET-1 accumulating in the culture medium in basal conditions or after UVB irradiation. Conversely, thiorphan, a specific inhibitor of neutral endopeptidase (NEP), rather increased the levels of ET-1 secretion mainly after UVB irradiation. Taken together, the results showed that normal human keratinocytes secrete and partly degrade ET-1 through ECE and NEP pathways and pointed out a differential regulation of ET-1 by UVB and UVA1 radiations without any noticeable role for PGE2.
Pernet
I
I
INSERM U346, Clinique Dermatologique, Hôpital E. Herriot, Lyon, France.
Mayoux
C
C
Trompezinski
S
S
Schmitt
D
D
Viac
J
J
D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics*; D016232:Endothelins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics*; D012867:Skin / Q000166:cytology; D015244:Thiorphan / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors; D015244:Thiorphan; D015232:Dinoprostone; C008890:phosphoramidon