LIGR, a protease-activated receptor-2-derived peptide, enhances skin pigmentation without inducing inflammatory processes

Authors

  • Connie B. Lin,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Nannan Chen,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Richard Scarpa,

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    • Present address: Ernst and Young LLP, 5 Times Square, New York, NY 10036, USA

  • Fei Guan,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Laura Babiarz-Magee,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Frank Liebel,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Wen-Hwa Li,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Menas Kizoulis,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Stanley Shapiro,

    1. The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A division of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA
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  • Miri Seiberg

    Corresponding authorSearch for more papers by this author

Address correspondence to Miri Seiberg, e-mail: mseiber@cpcus.jnj.com

Summary

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-NH2 (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-NH2 (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 [Ca2+] 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.

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