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Tumor necrosis factor alpha-mediated inhibition of melanogenesis is dependent on nuclear factor kappa B activation

Oncogene volume 18, pages 1553–1559 (1999)Cite this article

Abstract

Melanogenesis is a physiological process resulting in the synthesis of melanin pigments which play a crucial protective role against skin photocarcinogenesis. In vivo, solar ultraviolet light triggers the secretion of numerous keratinocyte-derived factors that are implicated in the regulation of melanogenesis. Among these, tumor necrosis factor α (TNFα), a cytokine implicated in the pro-inflammatory response, down-regulates pigment synthesis in vitro. In this report, we aimed to determine the molecular mechanisms by which this cytokine inhibits melanogenesis in B16 melanoma cells. First, we show that TNFα inhibits the activity and protein expression of tyrosinase which is the key enzyme of melanogenesis. Further, we demonstrate that this effect is subsequent to a down-regulation of the tyrosinase promoter activity in both basal and cAMP-induced melanogenesis. Finally, we present evidence indicating that the inhibitory effect of TNFα on melanogenesis is dependent on nuclear factor kappa B (NFκB) activation. Indeed, overexpression of this transcription factor in B16 cells is sufficient to inhibit tyrosinase promoter activity. Furthermore, a mutant of inhibitory kappa B (IκB), that prevents NFκB activation, is able to revert the effect of TNFα on the tyrosinase promoter activity. Taken together, our results clarify the mechanisms by which TNFα inhibits pigmentation and point out the key role of NFκB in the regulation of melanogenesis.

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References

  • Baeuerle PA and Henkel T. . 1994 Ann Rev Immunol. 12: 141–179.

  • Bennicelli JL and Guerry D. . 1993 Exp. Dermatol. 2: 186–190.

  • Bertolotto C, Bille K, Ortonne J-P and Ballotti R. . 1996 J. Cell. Biol. 134: 747–755.

  • Brenner DA, O'Hara M, Angel P, Chojkier M and Karin M. . 1989 Nature 337: 661–663.

  • Chakraborty AK, Funasaka Y, Slominski A, Ermak G, Hwang J, Pawelek JM and Ichihashi M. . 1996 Biochim. Biophys. Acta 1313: 130–138.

  • DiDonato JA, Mercurio F, Rosette F, Wu-Li C, Suyang H, Ghosh S and Karin M. . 1996 Mol. Cell. Biol. 16: 1295–1304.

  • Englaro W, Rezzonico R, Durand-Clément M, Lallemand D, Ortonne JP and Ballotti R. . 1995 J. Biol. Chem. 270: 24315–24320.

  • Gavrieli Y, Sherman Y and Ben-Sasson SA. . 1992 J. Cell. Biol. 119: 493–501.

  • Gilchrest BA, Park HY, Eller MS and Yaar M. . 1996 Photochem. Photobiol. 63: 1–10.

  • Gupta S, Campbell D, Dérijard B and Davis RJ. . 1995 Science 267: 389–393.

  • Hunt G, Todd C, Creswell JE and Thody AJ. . 1994 J. Cell. Sci. 107: 205–211.

  • Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner BM, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA and Peyron JF. . 1996 Cell 86: 787–798.

  • Inagaki Y, Truter S, Tanaka S, DiLiberto M and Ramirez F. . 1995 J. Biol. Chem. 270: 3353–3358.

  • Karin M. . 1995 J. Biol. Chem. 270: 16483–16486.

  • Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC and Luger TA. . 1990 J. Exp. Med. 172: 1609–1614.

  • Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, et al. 1994 Nature 372: 739–746.

  • Levine N, Sheftel SN, Eytan T, Dorr R, Hadley ME, Weinrach JC, Ertl GA, Toth K, McGee DL and Hurby VJ. . 1991 JAMA 226: 2730–2736.

  • Liou HC and Baltimore D. . 1993 Curr. Opin. Cell Biol. 5: 477–487.

  • Liu ZG, Hsu H, Goeddel DV and Karin M. . 1996 Cell 87: 565–576.

  • Martinez-Esparza M, Jimenez-Cervantes C, Beerman F, Aparicio P, Lozano JA and Garcia-Borron JC. . 1997 J. Biol. Chem. 272: 3967–3972.

  • Minden A, Lin A, McMahon M, Lange-carter C, Dérijard B, Davis R, Johnson GL and Karin M. . 1994 Science 266: 1719–1723.

  • O'Keefe F and Cuatrecasas P. . 1974 Proc. Natl. Acad. Sci. USA 71: 2500–2504.

  • Osborn L, Kunkel S and Nabel GJ. . 1989 Proc. Natl. Acad. Sci. USA 86: 2336–2340.

  • Oxholm A, Oxholm P, Staberg B and Bendtzen K. . 1988 Br. J. Dermatol. 118: 369–376.

  • Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ and Davis RJ. . 1995 J. Biol. Chem. 270: 7420–7426.

  • Swope VB, Abdel-Malek Z, Kassem LM and Nordlund JJ. . 1991 J. Invest. Dermatol. 96: 180–185.

  • Swope VB, Abdel-Malek ZA, Sauder DN and Nordlund JJ. . 1989 J. Immunol. 142: 1943–1949.

  • Takahashi H and Parsons PG. . 1992 J. Invest. Dermatol. 98: 481–487.

  • Tracey KJ and Cerami A. . 1993 Annu. Rev. Cell Biol. 9: 317–343.

  • Traenckner EB, Pahl HL, Henkel T, Schmidt KN, Wilk S and Baeuerle PA. . 1995 EMBO J. 14: 2876–2883.

  • Vandenabeele D, Declercq W, Beyaert R and Fiers W. . 1995 Trends Cell Biol. 5: 392–399.

  • Winston BW, Lange-Carter CA, Gardner AM, Johnson GL and Riches DWH. . 1995 Proc. Natl. Acad. Sci. USA 92: 1614–1618.

  • Yuan J. . 1997 Curr. Opin. Cell Biol. 9: 247–251.

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Acknowledgements

We thank A Grima and C Minghelli for illustration work, and C Sable for critical reading of the manuscript. This work was supported by Association pour la Recherche sur le Cancer (grant 9402), Ligue Contre le Cancer, Institut National de la Santé et de la Recherche Médicale and Université de Nice-Sophia Antipolis, Vaincre le Melanome Sanof.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM) U-385, France

    Walter Englaro, Philippe Bahadoran, Corine Bertolotto, Roser Buscà, Jean-Paul Ortonne & Robert Ballotti

  2. CJF 9605, Faculté de médecine, Avenue de Valombrose, 06107 Nice cedex 2, France

    Antonia Livolsi & Jean-François Peyron

  3. Centre de Biochimie, CNRS-UMR 134, Faculté des Sciences, Nice, 06018, France

    Benoit Dérijard

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  1. Walter Englaro
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Englaro, W., Bahadoran, P., Bertolotto, C. et al. Tumor necrosis factor alpha-mediated inhibition of melanogenesis is dependent on nuclear factor kappa B activation. Oncogene 18, 1553–1559 (1999). https://doi.org/10.1038/sj.onc.1202446

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