Advertisement

Der Hautarzt

, Volume 61, Issue 6, pp 478–486 | Cite as

Zur Bedeutung des Vitamin-D-Stoffwechsels in der humanen Haut

Eine aktuelle Standortbestimmung
  • L. Trémezaygues
  • J. Reichrath
Leitthema

Zusammenfassung

Vitamin-D-Mangel ist eine Endemie, von der weltweit schätzungsweise mehr als 1 Milliarde Menschen betroffen sind und an der in Deutschland ca. 60% der Bevölkerung leiden. In den letzten Jahren hat sich unser Verständnis über die wichtige Bedeutung des Vitamin-D-Stoffwechsels für den menschlichen Organismus entscheidend erweitert. Neben epidemiologischen Untersuchungen konnten In-vitro-Untersuchungen und Untersuchungen an Tiermodellen wichtige neue Funktionen von Vitamin D belegen, darunter auch potente immunmodulatorische und wachstumsregulierende Eigenschaften. Wir wissen daher heute, dass Vitamin-D-Mangel nicht nur mit einem erhöhten Risiko für Erkrankungen des Knochen- und Kalziumstoffwechsels, sondern auch mit einem erhöhten Risiko für zahlreiche weitere Erkrankungen (u. a. verschiedene Krebserkrankungen, kardiovaskuläre Erkrankungen, Infektionserkrankungen, Autoimmunerkrankungen) assoziiert ist. In diesem Beitrag wird der aktuelle Wissensstand zur Bedeutung des Vitamin-D-Stoffwechsels in der humanen Haut erörtert.

Schlüsselwörter

Vitamin D Humane Haut Antimikrobielle Peptide Hautkrebs Krebsprävention 

Abkürzungen

AMP

antimikrobielles Peptid

7-DHC

7-Dehydrocholesterol

IFN-γ

Interferon γ

1,25(OH)2D

1,25-Dihydroxyvitamin D3, Calcitriol

TNF-α

Tumornekrosefaktor α

VDR

Vitamin-D-Rezeptor

The significance of vitamin D metabolism in human skin

An update

Abstract

Vitamin D deficiency is endemic, affecting worldwide approximately more than 1 billion people and approximately 60% of the German population. In recent years, our understanding of the important role of vitamin D for human health has grown enormously. Epidemiological and in vitro investigations as well as animal studies have convincingly demonstrated new important functions of vitamin D, including potent immunoregulatory and growth regulatory properties. We know today that vitamin D deficiency/insufficiency is not exclusively associated with an increased risk for bone diseases, but with a multitude of other diseases (including various types of cancer, cardiovascular diseases, infectious diseases, and autoimmune diseases). We discuss our present understanding of the importance of the cutaneous vitamin D system.

Keywords

Vitamin D Human skin Antimicrobial peptides Skin cancer Cancer prevention 

Notes

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: J.R. Rednerhonorar von Fa. Diasorin.

Literatur

  1. 1.
    Holick MF (2007) Vitamin D deficiency. NEJM 357:266–281CrossRefPubMedGoogle Scholar
  2. 2.
    Hintzpeter B et al (2008) Vitamin D status and health correlates among German adults. Eur J Clin Nutr 62(9):1079–1089CrossRefPubMedGoogle Scholar
  3. 3.
    Trémezaygues L (2009) In vitro Untersuchungen in humanen Keratinozyten über mögliche protektive Eigenschaften von 1,25-Dihydroxyvitamin D3 gegen UVB- und niedrigdosierte ionisierende Strahlung. Promotionsarbeit an der Universität des SaarlandesGoogle Scholar
  4. 4.
    Lehmann B, Genehr T, Knuschke P et al (2001) UVB-induced conversion of 7-dehydrocholesterol to 1alpha25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. J Invest Dermatol 117:1179–1185CrossRefPubMedGoogle Scholar
  5. 5.
    Schlumpf M, Reichrath J, Lehmann B et al (in press) Fundamental questions to sun protection: a continuous education symposium at the University of Zürich on „Vitamin D, immune system and sun protection“. DermatoendocrinolGoogle Scholar
  6. 6.
    Holick MF, MacLaughlin JA, Clark MB, Holick SA et al (1980) Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210:203–205CrossRefPubMedGoogle Scholar
  7. 7.
    Bikle DD, Neumanic MK, Gee E, Elias P (1986) 1,25-Dihydroxyvitamin D3 production by human keratinocytes. J Clin Invest 78:557–566CrossRefPubMedGoogle Scholar
  8. 8.
    Holick MF (2003) Evolution and function of Vitamin D. Recent Results Cancer Res 164:3–28PubMedGoogle Scholar
  9. 9.
    Bikle DD, Halloran BP, Riviere JE (1994) Production of 1,25-Dihydroxyvitamin D3 by perfused pig skin. J Clin Invest 102:796–798Google Scholar
  10. 10.
    Lehmann B, Tiebel O, Meurer M (1999) Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents-a preliminary study. Arch Dermatol Res 291:507–510CrossRefPubMedGoogle Scholar
  11. 11.
    Fu GK, Lin D, Zhang MY et al (1997) Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol 11:1961–1970CrossRefPubMedGoogle Scholar
  12. 12.
    Seifert M, Tilgen W, Reichrath J (2009) Expression of vitamin D-1α-hydroxylase (1αOHase, CYP27B1) splicing variants in HaCaT keratinocytes and other skin cells: modulation by culture conditions and UV-B treatment in vitro. Anticancer Res 29(9):3659–3668PubMedGoogle Scholar
  13. 13.
    Henry HL (2001) The 25(OH)D/1,25(OH)2D3–24R-hydroxylase: a catabolic or biosynthetic enzyme? Steroids 66(3–5):391–398Google Scholar
  14. 14.
    Gniadecki R (1996) Stimulation versus inhibition of keratinocyte growth by 1,25-Dihydroxyvitamin D3: dependence on cell culture conditions. J Invest Dermatol 106(3):510–516CrossRefPubMedGoogle Scholar
  15. 15.
    Reichrath J, Müller SM, Kerber A et al (1997) Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin. J Am Acad Dermatol 36:19–28CrossRefPubMedGoogle Scholar
  16. 16.
    Reichrath J, Perez A, Chen TC et al (1997) The effectiveness of topical 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) application in the treatment of psoriasis: an immunohistological evaluation. Acta Derm Venereol (Stockh) 77:268–272Google Scholar
  17. 17.
    Holick MF, Reichrath J (1999) Clinical utility of 1,25-Dihydroxyvitamin D3 and its analogues for the treatment of psoriasis. In: Holick MF (Hrsg) Vitamin D: Physiology, molecular biologic and clinical aspects. The Humana Press Inc., Totowa New York, S 357–373Google Scholar
  18. 18.
    Reichrath J, Holick MF (n d) Psoriasis and other skin diseases. In: Feldman D, Glorieux FH, Pike JW (Hrsg) Vitamin D, 2nd edn. Academic, San Diego London Boston New York Sydney Tokyo TorontoGoogle Scholar
  19. 19.
    Van Etten E, Decallone B, Verlinden L et al (2003) Analogs of 1α,25-Dihydroxyvitamin D3 as pluripotent immunomodulators. J Cell Biochem 88:223–226CrossRefGoogle Scholar
  20. 20.
    Griffin M, Kumar R (2003) Effects of 1α,25-Dihydroxyvitamin D3 and its analogs on dendritic cell function. J Cell Biochem 88:323–326CrossRefPubMedGoogle Scholar
  21. 21.
    Adorini L, Penna G, Giarratana N, Uskokovic M (2003) Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem 88:227–233CrossRefPubMedGoogle Scholar
  22. 22.
    Solvoll K, Soyland E, Sandstad B, Drevon CA (2000) Dietary habits among patients with atopic dermatitis. Eur J Clin Nutr 54(2):93–97CrossRefPubMedGoogle Scholar
  23. 23.
    Heine G, Anton K, Henz BM, Worm M (2002) 1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro. Eur J Immunol 32(12):3395–3404PubMedGoogle Scholar
  24. 24.
    Katayama I, Minatohara K, Yokozeki H, Nishioka K (1996) Topical vitamin D3 downregulates IgE-mediated murine biphasic cutaneous reactions. Int Arch Allergy Immunol 111(1):71–76CrossRefPubMedGoogle Scholar
  25. 25.
    Homey B, Wang W, Soto H et al (2000) Cutting edge: The orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC). J Immunol 164:3465–3470PubMedGoogle Scholar
  26. 26.
    Gombard HF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 19(9):1067–1077CrossRefGoogle Scholar
  27. 27.
    Wang T-T, Nestel FP, Bourdeau V et al (2004) Cutting edge: 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173(5):2909–2912PubMedGoogle Scholar
  28. 28.
    Weber G, Heilborn JD, Chamorro Jimenez CI et al (2005) Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol 124(5):1080–1082CrossRefPubMedGoogle Scholar
  29. 29.
    Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75:39–48CrossRefPubMedGoogle Scholar
  30. 30.
    Zaiou M, Nizet V, Gallo RL (2003) Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. J Invest Dermatol 120:810–816CrossRefPubMedGoogle Scholar
  31. 31.
    Dorschner RA, Pestonjamasp VK, Tamakuwala S (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Invest Dermatol 117:91–97CrossRefPubMedGoogle Scholar
  32. 32.
    Frohm Nilsson M, Sandstedt B, Sørensen O et al (1999) The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 67:2561–2566Google Scholar
  33. 33.
    Peric M, Koglin S, Dombrowski Y et al (2009) Vitamin D analogs differentially control antimicrobial peptide/“alarmin“ expression in psoriasis. PLoS One 4(7):e6340CrossRefPubMedGoogle Scholar
  34. 34.
    De Haes P, Garmyn M, Degreef H et al (2003) 1,25-dihydroxyvitamin D3 inhibits ultraviolet B induced apoptosis, jun kinase actiation and interleukin-6 production in primary human keratinocytes. J Cell Biochem 89:663–673CrossRefGoogle Scholar
  35. 35.
    Lee JH, Youn JI (1998) The photoprotective effect of 1, 25-Dihydroxyvitamin D3 on ultraviolet B-induced damage in keratinocyte and its mechanisms of action. J Dermatol Sci 18:11–18CrossRefPubMedGoogle Scholar
  36. 36.
    Gupta R, Dixon KM, Deo SS et al (2006) Photoprotection by 1, 25-Dihydroxyvitamin D3 is associated by an increase in p53 and a decrease in nitric oxide products. J Invest Dermatol 127:707–715CrossRefPubMedGoogle Scholar
  37. 37.
    De Haes P, Garmyn M, Verstuyf A et al (2004) Two 14-epi analogues of 1, 25-dihydroxyvitamin D3 protect human keratinocytes against the effects of UVB. Arch Dermatol Res 295:527–534CrossRefGoogle Scholar
  38. 38.
    De Haes P, Garmyn M, Verstuyf A et al (2005) 1, 25(OH)2D3 and analogues protect primary human keatinocytes against UVB-induced DNA damage. J Photochem Photobiol B 78(2):141–148CrossRefGoogle Scholar
  39. 39.
    Trémezaygues L, Seifert M, Tilgen W, Reichrath J (in press) 1,25-dihydroxyvitamin D3 protects human keratinocytes against UV-B-induced damage: in vitro analysis of cell viability/proliferation, DNA-damage and –repair. DermatoendocrinolGoogle Scholar
  40. 40.
    Trémezaygues L, Seifert M, Vogt T et al (2010) 1,25-dihydroxyvitamin D3 modulates effects of ionizing radiation (IR) on human keratinocytes: in vitro analysis of cell viability/proliferation, DNA-damage and -repair. J Steroid Biochem Mol Biol (Epub ahead of print)Google Scholar
  41. 41.
    Osterlind A, Tucker MA, Stone BJ, Jensen OM (1988) The Danish case-control study of cutaneous malignant melanoma. II importance of UV-light exposure. Int J Cancer 42:319–324CrossRefPubMedGoogle Scholar
  42. 42.
    Garland CF, Comstock GW, Garland FC et al (1989) Serum 25-hydroxyvitamin D and colon cancer: eight year prospective study. Lancet 2(8673):1176–1178CrossRefPubMedGoogle Scholar
  43. 43.
    Grant WB (2002) An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 94:1867–1875CrossRefPubMedGoogle Scholar
  44. 44.
    Nürnberg B, Gräber S, Gärtner B et al (2009) Reduced serum 25-Hydroxyvitamin D levels in stage IV melanoma patients. Anticancer Res 29:3669–3674PubMedGoogle Scholar
  45. 45.
    Newton-Bishop JA, Beswick S, Randerson-Moor J et al (2009) Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. J Clin Oncol 27(32):5439CrossRefPubMedGoogle Scholar
  46. 46.
    Hutchinson PE, Osborne JE, Lear JT et al (2000) Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma. Clin Cancer Res 6(2):498–504PubMedGoogle Scholar
  47. 47.
    Bastuji-Garin S, Diepgen TL (2002) Cutaneous malignant melanoma, sun exposure and sunscreen use: epidemiological evidence. Br J Dermatol146(Suppl 61):24–30Google Scholar
  48. 48.
    Reichrath J (2003) Protecting against adverse effects of sun protection? J Am Acad Dermatol 49(6):1204–1206CrossRefPubMedGoogle Scholar
  49. 49.
    Reichrath J, Querings K (2004) Vitamin D deficiency needs to be detected and treated in solid-organ transplant recipients (OTRs). Dermatol Surg 30(12):1501–1501CrossRefPubMedGoogle Scholar
  50. 50.
    Querings K, Reichrath J (2004) A plea for detection and treatment of vitamin D deficiency in patients under photoprotection, including patients with xeroderma pigmentosum and basal cell nevus syndrome. Cancer Cause Control 15(2):219CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Klinik für Dermatologie, Venerologie und Allergologie, Hautklinik und PoliklinikUniversitätsklinikum des SaarlandesHomburg/SaarDeutschland

Personalised recommendations