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Constitutive Expression of MC1R in HaCaT Keratinocytes Inhibits Basal and UVB-induced TNF-α Production

Authors

  • Geneviève Garcin,

    1. CNRS, UMR 5247 (IBMM), Faculté de Pharmacie, Université Montpellier I, Montpellier, France
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  • Lionel Le Gallic,

    1. Laboratoire d’Histologie, Embryologie, Cytogénétique, UFR de Médecine, Université Montpellier I, Nîmes, France
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  • Pierre-Emmanuel Stoebner,

    1. CNRS, UMR 5247 (IBMM), Faculté de Pharmacie, Université Montpellier I, Montpellier, France
    2. Department of Dermatology, Groupe Hospitalo-Universitaire Caremeau, Nîmes, France
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  • Anne Guezennec,

    1. YSL Recherche et Développement, Neuilly sur Seine, France
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  • Joelle Guesnet,

    1. YSL Recherche et Développement, Neuilly sur Seine, France
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  • Thierry Lavabre-Bertrand,

    1. Laboratoire d’Histologie, Embryologie, Cytogénétique, UFR de Médecine, Université Montpellier I, Nîmes, France
    2. Laboratoire de Cytologie Clinique et Cytogénétique, Groupe Hospitalo-Universitaire Caremeau, Nîmes, France
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  • Jean Martinez,

    1. CNRS, UMR 5247 (IBMM), Faculté de Pharmacie, Université Montpellier I, Montpellier, France
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  • Laurent Meunier

    Corresponding author
    1. CNRS, UMR 5247 (IBMM), Faculté de Pharmacie, Université Montpellier I, Montpellier, France
    2. Department of Dermatology, Groupe Hospitalo-Universitaire Caremeau, Nîmes, France
      *Corresponding author email: laurent.meunier@chu-nimes.fr (L. Meunier)
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*Corresponding author email: laurent.meunier@chu-nimes.fr (L. Meunier)

Abstract

Alpha-melanocyte stimulating hormone (α-MSH) binds to melanocortin-1 receptor (MC1R) on melanocytes to stimulate pigmentation and modulate various cutaneous inflammatory responses. MC1R expression is not restricted to melanocytic cells and may be induced in keratinocytes after UVB exposure. We hypothesized that MC1R signaling in keratinocytes, wherein basal conditions are barely expressed, may modulate mediators of inflammation, such as nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α). Therefore, we generated HaCaT cells that stably express human MC1R or the Arg151Cys (R151C) nonfunctional variant. We demonstrate that: (1) the constitutive activity of MC1R results in elevated intracellular cAMP level, reduced NF-κB activity and decreased TNF-α transcription; (2) binding of α-MSH to MC1R and the subsequent increase in cAMP production do not inhibit TNFα-mediated NF-κB activation; (3) MC1R signaling is sufficient to strongly inhibit UVB-induced TNF-α expression and this inhibitory effect is further enhanced by α-MSH stimulation. Our findings suggest that the constitutive activity of the G-protein-coupled MC1R in keratinocytes may contribute to the modulation of inflammatory events and immune response induced by UV light.

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