Skip to main content
Log in

Inhibitory effect of 1α,25-dihydroxyvitamin D3 on mast cell proliferation and A23187-induced histamine release, also accompanied by a decreased c-kit receptor

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Using mouse peritoneal mast cells, we investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on mast cell proliferation and histamine release. Calcitriol did not affect IL-3/IL-4-dependent mast cell proliferation, but it selectively inhibited stem cell factor-dependent mast cell proliferation and colony formation. Immunohistochemical and immunoblot analyses revealed that calcitriol treatment reduced expression of purified peritoneal mast cell c-kit protein. Using a mast cell line, MC/9, both c-kit protein and c-kit mRNA transcript were seen to be reduced following calcitriol treatment. Calcitriol also reduced histamine release induced by calcium ionophore A23187. In contrast, anti-IgE antibody-dependent histamine release was not affected by calcitriol. Our results indicate that calcitriol inhibits mast cell proliferation and A23187-induced histamine release that might be associated with a decreased expression of c-kit receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Toyota N, Kitamura Y, Ogawa K (1990) Administration of 8-methoxypsolaren and ultraviolet A irradiation (PUVA) induces turnover of mast cells in the skin of C57BL/6 mice. J Invest Dermatol 95:353–358

    Article  PubMed  CAS  Google Scholar 

  2. Toyota N, Hashimoto Y, Matsuo S, Izuka H (1995) Transforming growth factor β 1 inhibits IL-3 and IL-4-dependent mouse connective tissue-type mast cell proliferation. Arch Dermatol Res 287:198–201

    Article  PubMed  CAS  Google Scholar 

  3. Toyota N, Hashimoto Y, Matsuo S, Kitamura Y, Iizuka H (1996) Effects of FK506 and cyclosporin A on proliferation, histamine release and phenotype of murine mast cells. Arch Dermatol Res

  4. Bienenstock J, Befus AD, Pearse F, Denburg J, Goodacre R (1982) Mast cell heterogeneity: derivation and function, with emphasis on the intestine. J Allergy Clin Immunol 70:407–412

    Article  PubMed  CAS  Google Scholar 

  5. Galli SJ, Dvorak AM, Dvorak HF (1984) Basophil and mast cell: morphologic insights into their biology, secretory patterns, and function. Prog Allergy 34:1–141

    PubMed  CAS  Google Scholar 

  6. Tsuji K, Nakahata T, Takagi M, Kobayashi T, Ishiguro A, Kikuchi T, Naganuma K, Koike K, Miyajima A, Arai K, Akabane T (1990) Effects of interleukin-3 and interleukin-4 on the development of “connective-tissue type” mast cells: interleukin-3 supports their survival and interleukin-4 triggers and support their proliferation synergistically with interleukin-3. Blood 75:421–427

    PubMed  CAS  Google Scholar 

  7. Hamaguchi Y, Kanakura Y, Fujita J, Takeda S, Nakano T, Tarui S, Honjo T, Kitamura Y (1987) Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissuetype mast cells. J Exp Med 165:268–273

    Article  PubMed  CAS  Google Scholar 

  8. Nabel GS, Galli J, Dvorak AM, Dvorak HF, Cantor H (1981) Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells. Nature 291:332–334

    Article  PubMed  CAS  Google Scholar 

  9. Thompson-Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, Rennick DM (1991) Interleukin 10: A novel stimulatory factor for mast cells and progenitors. J Exp Med 173:507–510

    Article  PubMed  CAS  Google Scholar 

  10. Hültner L, Druez C, Moeller J, Uyttenhove C, Schmitt E, Rude E, Dormer P, Van Snick J (1990) Mast cell growth enhancing activity (MEA) is a structurally related and functionally identical to p40/TCGF III (interleukin 9). Eur J Immunol 20:1413–1416

    PubMed  Google Scholar 

  11. Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hsu R-Y, Birkett NC, Okino KH, Murdock DC, Jacobsen FW, Langley KE, Smith KA, Takeishi T, Cattanach BM, Galli SJ, Suggs SV (1990) Stem cell factor is encoded at the SL locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63:213–224

    Article  PubMed  CAS  Google Scholar 

  12. Besmer P, Murphy JE, George PC, Qiu F, Bergold PJ, Lederman L, Snyder HW, Brodeur D, Zukkerman EE, Hardy WD (1986) A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature 320:415–421

    Article  PubMed  CAS  Google Scholar 

  13. Qiu F, Ray P, Brown K, Barker PE, Jhanwar S, Ruddle FH, Besmer P (1988) Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family-oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J 7:1003–1011

    PubMed  CAS  Google Scholar 

  14. Kuroki T (1985) Possible functions of 1,25-dihydroxyvitamin D3, an active form of vitamin D3, in the differentiation and development of skin. J Invest Dermatol 84:459–460

    Article  PubMed  CAS  Google Scholar 

  15. Smith EL, Walworth NC, Holick MF (1986) Effect of 1α,25-dihydroxyvitamin D3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions. J Invest Dermatol 86:709–714

    Article  PubMed  CAS  Google Scholar 

  16. Hosomi J, Hosoi J, Abe E, Suda T, Kuroki T (1983) Regulation of terminal differentiation of cultured mouse epidermal cells by 1α,25-dihydroxyvitamin D3. Endocrinology 113:1950–1957

    Article  PubMed  CAS  Google Scholar 

  17. Itin PH, Pittelkow MR, Kumar R (1994) Effects of vitamin D metabolites on proliferation and differentiation of cultured human epidermal keratinocytes grown in serum-free or defined culture medium. Endocrinology 135:1793–1798

    Article  PubMed  CAS  Google Scholar 

  18. Pike JW (1991) Vitamin D3 receptors: structure and function in transcription. Annu Rev Nutr 11:189–216

    Article  PubMed  CAS  Google Scholar 

  19. Nakahata T, Ogawa M (1982) Identification in culture of a class of hematopoietic colony-forming units with extensive capacity to self-renew and generate multipotential hematopoietic colonies. Proc Natl Acad Sci USA 79:3843–3847

    Article  PubMed  CAS  Google Scholar 

  20. Tsuji K, Zsebo KM, Ogawa M (1991) Murne mast cell colony formation supported by IL-3, IL-4, and recombinant rat stem cell factor, ligand for c-kit. J Cell Physiol 148:362–369

    Article  PubMed  CAS  Google Scholar 

  21. Ogawa M, Matsuzaki Y, Nishikawa S, Hayashi S, Kunusada T, Nakauchi H, Nishikawa S (1991) Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med 174:63–71

    Article  PubMed  CAS  Google Scholar 

  22. Nishikawa S, Kusakabe M, Yoshinaga K, Ogawa M, Hayashi S, Kunusada T, Era T, Sakakura T, Nishikawa S (1991) In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit dependency during melanocyte development. EMBO J 10:2111–2118

    PubMed  CAS  Google Scholar 

  23. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  24. Maniatis T, Fritsch EF, Sambrook T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

    Google Scholar 

  25. Thomas PS (1980) Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA 77:5201–5205

    Article  PubMed  CAS  Google Scholar 

  26. Saito H, Okajima F, Moki TFP, Sha’afi RI, Ui M (1988) Effect of cholera toxin on histamine release from bone marrow-derived mouse mast cells. Proc Natl Acad Sci USA 85: 2504–2508

    Article  PubMed  CAS  Google Scholar 

  27. Pearce FL (1982) Calcium and histamine secretion from mast cells. Prog Med Chem 19:59–109

    PubMed  CAS  Google Scholar 

  28. Caroni P, Gazzotti P, Vuilleumier P, Simon W, Carafori E (1977) Ca2+ transport mediated by synthetic neutral Ca2+-ionophore in biological membranes. Biochimica Biophys Acta 470: 437–445

    CAS  Google Scholar 

  29. Matsue H, Cruz PD Jr, Bergstresser PR, Takashima A (1992) Cytokine expression by epidermal subpopulations. J Invest Dermatol 99:42S-45S

    Article  PubMed  CAS  Google Scholar 

  30. Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP Paul WE (1989) Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon or to calcium ionophores. Nature 339:64–67

    Article  PubMed  CAS  Google Scholar 

  31. Brown MA, Pierce JH, Watson CJ, Falco J, Ihle JN, Paul WE (1987) B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell 50:807–818

    Google Scholar 

  32. Galli SJ, Tsai M, Wershil BK (1993) The c-kit receptor, stem cell factor, and mast cells: what each is teaching us about the other. Am J Pathol 142:965–974

    PubMed  CAS  Google Scholar 

  33. Grabbe J, Welker P, Dippel B, Crarnetzki BM (1994) Stem cell factor, a novel cutaneous growt factor for mast cells and melanocytes. Arch Dermatol Res 287:78–84

    Article  PubMed  CAS  Google Scholar 

  34. Fujita J, Nakayama H, Onoue H, Kanakura Y, Nakano T, Asai H, Takeda S, Honjo T, Kitamura Y (1988) Fibroblast-dependent growth of mouse mast cells in vitro: duplication of mast cell depletion in mutant mice of W/Wv genotype. J Cell Physiol 134:78–84

    Article  PubMed  CAS  Google Scholar 

  35. Keller R, Hess MW, Riley JF (1976) Mast cells in the skin or normal, hairless and athymic mice. Experientia 32:171–172

    Article  PubMed  CAS  Google Scholar 

  36. Koli K, Keski-Oja J (1993) Vitamin D3 and calcipotriol enhance the secretion of transforming growth factor-β1 and-β2 in cultured murine keratinocytes. Growth Factors 8:153–163

    PubMed  CAS  Google Scholar 

  37. Koga M, Elisman JA, Sutherland RL (1988) Regulation of epidermal growth factor receptor levels by 1,25-dihydroxyvitamin D3 in human breast cancer cells. Cancer Res 48:2734–2739

    PubMed  CAS  Google Scholar 

  38. Matsumoto K, Hashimoto K, Nishida Y, Hashiro M, Yoshikawa K (1990) Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal human keratinocytes cultured in serumfree medium. Biochem Biophys Res Commun 166:916–923

    Article  PubMed  CAS  Google Scholar 

  39. Pillai S, Bikle DD, Elias P (1988) 1,25-dihydroxyvitamin D production and receptor binding in human keratinocytes varies with differentiation. J Biol Chem 263:5390–5395

    PubMed  CAS  Google Scholar 

  40. Bikle DD, Nemanic MK, Gee E, Elias P (1986) 1,25-dihydroxyvitamin D production by human keratinocyte. J Clin Invest 78:557–566

    Article  PubMed  CAS  Google Scholar 

  41. Inaba M, Burgos-Trinidad M, DeLÖuca HF (1991) Characteristics of the 25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3-24-hydroxylase(s) from HL-60 cells. Arch Biochem Biophys 284:257–263

    Article  PubMed  CAS  Google Scholar 

  42. Bittner B, Bleehen SS, MacNeil S (1991) I alpha, 25(OH)2 vitamin D3 increases intracellular calcium in human keratinocytes. Br J Dermatol 124:230–235

    Article  Google Scholar 

  43. Hills SE, Bleehen SS, MacNeil S (1989) 1α,25-dihydroxyvitamin D3 increases intracellular free calcium in murine B16 melanoma. Br J Dermatol 120:21–30

    Article  Google Scholar 

  44. Janiszewski J, Hizinga JD, Blennerhassett MG (1992) Mast cell ionic channels: significance for stimulus-secretion coupling. Can J Physiol Pharmacol 70:1–7

    PubMed  CAS  Google Scholar 

  45. Zhang L, McCloskey MA (1995) Immunoglobulin E receptor-activated calcium conductance in rat mast cell. J Physiol 483: 59–66

    PubMed  CAS  Google Scholar 

  46. Coleman JW, Holliday MR, Kimber I, Zsebo KM, Galli SJ (1993) Regulation of mouse peritoneal mast cell secretory function by stem cell factor, IL-3 or IL-4. J Immunol 150:556–562

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toyota, N., Sakai, H., Takahashi, H. et al. Inhibitory effect of 1α,25-dihydroxyvitamin D3 on mast cell proliferation and A23187-induced histamine release, also accompanied by a decreased c-kit receptor. Arch Dermatol Res 288, 709–715 (1996). https://doi.org/10.1007/BF02505282

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02505282

Key words

Navigation