Advertisement

Archives of Dermatological Research

, Volume 288, Issue 7, pp 366–372 | Cite as

Epidermal differentiation characteristics of the psoriatic plaque during treatment with calcipotriol

  • C. J. M. van der Vleuten
  • E. M. G. J. de Jong
  • P. C. M. van de Kerkhof
Original Paper

Abstract

Treatment of psoriasis with vitamin D3 analogues is well established in present dermatological practice. One of the clinical sings of the psoriatic plaque that reduces early and markedly during treatment with the vitamin D3 analogue calcipotriol is scaling. Since scaling is the clinical manifestation of disordered epidermal differentiation, early changes in immunohistochemical markers for differentiation (transglutaminase, involucrin and filaggrin) were studied in patients who had been treated with calcipotriol for 4 weeks. Markers for proliferation (Ki-67 antigen) and inflammation (polymorphomuclear leucocytes and T lymphocytes) were also studied and correlated with the differentiation characteristics. Clinically, a major improvement was seen in all patients. A significant decrease in the percentage of transglutaminase-positive cell layers was observed during the first week of treatment. In contrast, an increase in transglutaminase activity in epidermal cell cultures following incubation with calcipotriol has been reported. Involucrin expression was only slightly modulated in vivo. However, a major restoration of the filaggrin-positive cell layer and significant reduction in the recruitment of cycling epidermal cells characterized the epidermal response to calcipotriol treatment. Markers for inflammation (T11-positive cells and elastase-positive cells) were also reduced substantially during the first week of treatment with calcipotriol. From this study it may be concluded that inhibition of epidermal growth and recovery of the filaggrin-positive cell layer are among the in vivo effects of calcipotriol.

Key words

Immunohistochemistry Psoriasis Calcipotriol Epidermal differentiation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Berth Jones J, Hutchinson PE (1992) Vitamin D analogues and psoriasis. Br J Dermatol 127:71–78PubMedCrossRefGoogle Scholar
  2. 2.
    Kragballe K, Wildfang IL (1990) Calcipotriol (MC 903), a novel vitamin D3 analogue stimulates terminal differentiation and inhibits proliferation of cultured human keratinocytes. Arch Dermatol Res 282:164–167PubMedCrossRefGoogle Scholar
  3. 3.
    Smith EL, Walworth NC, Holick MF (1986) Effect of 1 alpha, 25-dihydroxyvitamin D3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions. J Invest Dermatol 86:709–714PubMedCrossRefGoogle Scholar
  4. 4.
    Gerritsen MJ, Boezeman JB, Vlijmen Willems IM van, Kerkhof PC van de (1994) The effect of tacalcitol (1,24(OH)2D3) on cutaneous inflammation, epidermal proliferation and keratinization in psoriasis: a placebo-controlled, double-blind study. Br J Dermatol 131:57–63PubMedCrossRefGoogle Scholar
  5. 5.
    Gerritsen MJ, Rulo HF, Vlijmen Willems I van, Erp PE van, Kerkhof PC van de (1993) Topical treatment of psoriatic plaques with 1,25-dihydroxyvitamin D3: a cell biological study. Br J Dermatol 128:666–673PubMedCrossRefGoogle Scholar
  6. 6.
    Jong EM de, Kerkhof PC van de (1991) Simultaneous assessment of inflammation and epidermal proliferation in psoriatic plaques during long-term treatment with the vitamin D3 analogue MC903: modulations and interrelations. Br J Dermatol 124:221–229PubMedCrossRefGoogle Scholar
  7. 7.
    Bagot M, Charue D, Lescs MC, Pamphile RP, Revuz J (1994) Immunosuppressive effects of 1,25-dihydroxyvitamin D3 and its analogue calcipotriol on epidermal cells. Br J Dermatol 130: 424–431PubMedCrossRefGoogle Scholar
  8. 8.
    Hosomi J, Hosoi J, Abe E, Suda T, Kuroki T (1983) Regulation of terminal differentiation of cultured mouse epidermal cells by 1 alpha,25-dihydroxyvitamin D3. Endocrinology 113:1950–1957PubMedCrossRefGoogle Scholar
  9. 9.
    Regnier M, Darmon M (1991) 1,25-Dihydroxyvitamin D3 stimulates specifically the last steps of epidermal differntiation of cultured human keratinocytes. Differentiation 47:173–188PubMedCrossRefGoogle Scholar
  10. 10.
    Lee SC, Ikai K, Ando Y, Imamura S (1989) Effects of 1 alpha,25-dihydroxyvitamin D3 on the transglutaminase activity of transformed mouse epidermal cells in culture. J Dermatol 16: 7–11PubMedGoogle Scholar
  11. 11.
    Sebag M, Gulliver W, Kremer R (1994) Effect of 1,25 dihydroxyvitamin D3 and calcium on growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes. J Invest Dermatol 103:323–329PubMedCrossRefGoogle Scholar
  12. 12.
    Su MJ, Bikle DD, Mancianti ML, Pillai S (1994) 1,25-Dihydroxyvitamin D3 potentiates the keratinocyte response to calcium. J Biol Chem 269:14723–14729PubMedGoogle Scholar
  13. 13.
    Duijnhoven J van, Schalkwijk J, Kranenborg M, Vlijmen Willems I Van et al. (1992) MON-150, a versatile monoclonal antibody against involucrin: characterization and applications. Arch Dermatol Res 284:167–172PubMedCrossRefGoogle Scholar
  14. 14.
    Synkowski D, Provost T (1982) Enumeration of T-cell subhopulations in lupus erythematosus lesions using monoclonal anti-bodies. Clin Res 30:611AGoogle Scholar
  15. 15.
    Vleuten CJ van der, Kroot EJ, Jong EM de, Kerkhof PC van de (1996) The immunohistochemical effects of a single challenge with intermediate dose ultraviolet B on normal human skin. Arch Dermatol Res (in press)Google Scholar
  16. 16.
    Erp PE van, Mare S de, Rijzewijk JJ, Kerkhof PC van de, Bauer FW (1989) A sequential double immunoenzymic staining procedure to obtain cell kinetic information in normal and hyperproliferative epidermis. Histochem J 21:343–347PubMedCrossRefGoogle Scholar
  17. 17.
    Ramsay CA, Berth Jones J, Brundin G, Cunliffe WJ, Dubertret L, Kerkhof PC van de, Menne T, Wegmann E (1994) Long-term use of topical calcipotriol in chronic plaque psoriasis. Dermatology 189:260–264PubMedCrossRefGoogle Scholar
  18. 18.
    Mare S de, Jong EG de, Kerkhof PC van de (1990) DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 analogue MC903 and betamethasone. Br J Dermatol 123:291–295PubMedCrossRefGoogle Scholar
  19. 19.
    Holland DB, Roberts SG, Russell A et al. (1990) Changes in epidermal keratin levels during treatment of psoriasis with the topical vitamin D3 analogue MC903. (abstract). Br J Dermatol 122:284Google Scholar
  20. 20.
    Verburgh CA, Nieboer C (1989) Local application of vitamin D3 pderivative MC903 in psoriasis: influence on cellular infiltrate, Langerhans cells and keratinocyte markers (abstract). J Invest Dermatol 93:310Google Scholar
  21. 21.
    Peterson LL, Zettergren JG, Wuepper KD (1983) Biochemistry of transglutaminases and cross-linking in the skin. J Invest Dermatol 81:95s-100sPubMedCrossRefGoogle Scholar
  22. 22.
    Watt FM (1983) Involucrin and other markers of keratinocyte terminal differentiation. J Invest Dermatol 81:100s-103sPubMedCrossRefGoogle Scholar
  23. 23.
    Hohl D (1993) Expression patterns of loricrin in dermatological disorders. Am J Dermatopathol 15:20–27PubMedCrossRefGoogle Scholar
  24. 24.
    Zettergren JG, Peterson LL, Wuepper KD (1984) Keratolinin: the soluble substrate of epidermal transglutaminase from human and bovine tissue. Proc Natl Acad Sci USA 81:238–242PubMedCrossRefGoogle Scholar
  25. 25.
    Michel S, Dermachez M (1988) Localization and in vivo activity of epidermal transglutaminase. J Invest Dermatol 90:472–474PubMedCrossRefGoogle Scholar
  26. 26.
    Nonomura K, Yamanishi K, Hosokawa Y, Doi H, Hirano J, Fukushima S, Yasuno H (1993) Localization of transglutaminase 1 mRNA in normal and psoriatic epidermis by non-radioactive in situ hybridization. Br J Dermatol 128:23–28PubMedCrossRefGoogle Scholar
  27. 27.
    Gerritsen MJ, Erp PE van, Kerkhof PC van de (1995) Transglutaminase positive cells in psoriatic epidermis during treatment with calcitriol (1α,25 dihydroxy vitamin D3) and tacalcitol (1α,24 dihydroxy vitamin D3). Br J Dermatol 133:656–659PubMedCrossRefGoogle Scholar
  28. 28.
    Esmann J, Voorhees JJ, Fisher GJ (1989) Increased membrane-associated transglutaminase activity in psoriasis. Biochemi Biophys Res Commun 164:219–224CrossRefGoogle Scholar
  29. 29.
    Schroeder WT, Thacher SM, Stewart Galetka S, Annarella M, Chema D, Siciliano MJ, Davies PJ, Tang HY, Sowa BA, Duvic M (1992) Type I keratinocyte transglutaminase: expression in human skin and psoriasis. J Invest Dermatol 99:27–34PubMedCrossRefGoogle Scholar
  30. 30.
    Dale BA, Holbrook KA, Steinert PM (1978) Assembly of stratum corneum basic protein and keratin filaments in macrofibrils. Nature 276:729–731PubMedCrossRefGoogle Scholar
  31. 31.
    Jong EM de, Vlijmen IM van, Erp PE van, Ramaekers FC, Troyanovski SM, Kerkhof PC van de (1991) Keratin 17: a useful marker in anti-psoriatic therapies. Arch Dermatol Res 283: 480–482PubMedCrossRefGoogle Scholar
  32. 32.
    Kerkhof PC van de (1995) Biological activity of vitamin D analogues in the skin, with special reference to antipsoriatic mechanisms. Br J Dermatol 132:675–682PubMedCrossRefGoogle Scholar
  33. 33.
    Gerritsen MJ, Elbers M, Jong EM de, Kerkhof PC van de (1996) Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin. J Dermatol (in press)Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • C. J. M. van der Vleuten
    • 1
  • E. M. G. J. de Jong
    • 1
  • P. C. M. van de Kerkhof
    • 1
  1. 1.Department of DermatologyUniversity Hospital NijmegenNijmegenThe Netherlands

Personalised recommendations