Inhibition of melanosome transfer results in skin lightening

Citation
M. Seiberg et al., Inhibition of melanosome transfer results in skin lightening, J INVES DER, 115(2), 2000, pp. 162-167
Citations number
21
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022202X → ACNP
Volume
115
Issue
2
Year of publication
2000
Pages
162 - 167
Database
ISI
SICI code
0022-202X(200008)115:2<162:IOMTRI>2.0.ZU;2-0
Abstract
The chemical basis of melanogenesis is well documented, but the mechanism o f melanosome transfer and the regulation of pigmentation by keratinocyte-me lanocyte interactions are not well understood. Therefore we examined the ef fects of serine protease inhibitors on skin pigmentation and found that the protease-activated receptor 2, expressed on keratinocytes, may regulate pi gmentation via keratinocyte-melanocyte interactions. Here we show that modu lation of protease-activated receptor 2 activation affects melanosome trans fer into keratinocytes, resulting in changes in pigment production and depo sition. SLIGRL, the protease-activated receptor 2 activating peptide, enhan ced melanosome ingestion by keratinocytes, thus increasing pigment depositi on. RWJ-50353, a serine protease inhibitor, led to reduced pigment depositi on in melanocytes and depigmentation. Electron microscopy studies illustrat ed an accumulation of immature melanosomes inside melanocytes and abnormal dendrite dynamics in RWJ-50353-treated epidermal equivalents. RWJ-50353 ind uced a visible and dose-dependent skin lightening effect in the dark-skinne d Yucatan swine. Examinations by electron microscopy indicated that the in vivo transfer of melanosomes from melanocytes to keratinocytes was affected . Our data suggest that modulation of keratinocyte-melanocyte interactions via the protease-activated receptor 2 pathway affects melanosome transfer. The use of RWJ-50353 to modulate protease-activated receptor 2 activation c ould lead to a new class of depigmenting agents.