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Modulation of endothelin‐1 in normal human keratinocytes by UVA1/B radiations, prostaglandin E2 and peptidase inhibitors
Author(s) -
Pernet I.,
Mayoux C.,
Trompezinski S.,
Schmitt D.,
Viac J.
Publication year - 2000
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2000.009006401.x
Subject(s) - thiorphan , phosphoramidon , prostaglandin e2 , secretion , neprilysin , endothelin 1 , hacat , chemistry , endothelin receptor , prostaglandin , endocrinology , medicine , biology , microbiology and biotechnology , enzyme , biochemistry , receptor , in vitro
In the skin, keratinocytes synthesize and secrete endothelin‐1 (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.