LIGR, a protease-activated receptor-2-derived peptide, enhances skin pigmentation without inducing inflammatory processes.
The protease-activated receptor-2 (PAR-2) is a seven transmembrane G-protein-coupled receptor that could be activated by serine protease cleavage or by synthetic peptide agonists. We showed earlier that activation of PAR-2 with Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLIGRL), a known PAR-2 activating peptide, induces keratinocyte phagocytosis and increases skin pigmentation, indicating that PAR-2 regulates pigmentation by controlling phagocytosis of melanosomes. Here, we show that Leu-Ile-Gly-Arg-NH(2) (LIGR) can also induce skin pigmentation. Both SLIGRL and LIGR increased melanin deposition in vitro and in vivo, and visibly darkened human skins grafted onto severe combined immuno-deficient (SCID) mice. Both SLIGRL and LIGR stimulated Rho-GTP activation resulting in keratinocyte phagocytosis. Interestingly, LIGR activates only a subset of the PAR-2 signaling pathways, and unlike SLIGRL, it does not induce inflammatory processes. LIGR did not affect many PAR-2 signaling pathways, including [Ca(2+)] mobilization, cAMP induction, the induction of cyclooxgenase-2 (COX-2) expression and the secretion of prostaglandin E2, interleukin-6 and -8. PAR-2 siRNA inhibited LIGR-induced phagocytosis, indicating that LIGR signals via PAR-2. Our data suggest that LIGR is a more specific regulator of PAR-2-induced pigmentation relative to SLIGRL. Therefore, enhancing skin pigmentation by topical applications of LIGR may result in a desired tanned-like skin color, without enhancing inflammatory processes, and without the need of UV exposure.
Lin
Connie B
CB
The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA.
Chen
Nannan
N
Scarpa
Richard
R
Guan
Fei
F
Babiarz-Magee
Laura
L
Liebel
Frank
F
Li
Wen-Hwa
WH
Kizoulis
Menas
M
Shapiro
Stanley
S
Seiberg
Miri
M
D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D010587:Phagocytosis; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012880:Skin Pigmentation / Q000187:drug effects*; D016038:Skin Transplantation; D013552:Swine; D014183:Transplantation, Heterologous
D010455:Peptides; D044464:Receptor, PAR-2