Journal Mobile Options
Table of Contents
Vol. 14, No. 4, 2001
Issue release date: July–August 2001

Tacalcitol, an Active Vitamin D3, Induces Nerve Growth Factor Production in Human Epidermal Keratinocytes

Fukuoka M. · Sakurai K. · Ohta T. · Kiyoki M. · Katayama I.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


The human epidermal keratinocyte cell line K-TL-1, developed from a benign epidermal tumor, was cultured in the presence of the synthetic vitamin D3 analogue tacalcitol [1α,24(R)-dihydroxyvitamin D3] to assess the effects on the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured with 10–8M of tacalcitol. Supernatants and cell homogenates were collected and NGF concentrations were determined by enzyme-linked immunosorbent assay. The concentration of NGF in the supernatants of cultures treated with tacalcitol peaked within 24 h after the start of tacalcitol treatment and remained stable for 96 h. This NGF induction caused by tacalcitol was dose-dependent, showing an ED50 between 10–10 and 10–9M. Induction of NGF mRNA expression by tacalcitol was also observed by RT-PCR, indicating that tacalcitol induced NGF expression through transcriptional activation. These results suggest that active vitamin D3 could treat peripheral neuropathy by inducing NGF production in the skin.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Longo FM, Holtzman DM, Grimes ML, Mobley WC: NGF: Actions in the peripheral and central nervous systems; in Loughlin SE, Fallon JH (eds): Neurotrophic Factors. San Diego, Academic Press, 1993, pp 209–256.
  2. DiStefano PS, Friedman B, Radziejewski C, Alexander C, Boland P, Schick CM, Lindsay RM, Wiegand SJ: The neurotrophins BDNF, NT-3, and NGF display distinct pattern of retrograde axonal transport in peripheral and central neurons. Neuron 1992;8:983–993.
  3. Hellweg R, Wohrle M, Hartung HD, Stracke H, Hock C, Federlin K: Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation. Neurosci Lett 1991;125:1–4.
  4. Lewen G, Mendell LM: Nerve growth factor and nociception. Trends Neurosci 1993;16:353–359.
  5. Apfel SC, Arezzo JC, Brownlee M, Federoff H, Kessler JA: Nerve growth factor protects against experimental diabetic sensory neuropathy. Brain Res 1994;634:7–12.
  6. Apfel SC, Lipton RB, Arezzo JC, Kessler JA: Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 1991;29:87–90.
  7. Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut RE, Sinicropi DV: The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med 1996;6:703–707.
  8. Albers KM, Wright DE, Davis BM: Over expression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J Neurosci 1994;14:1422–1432.
  9. Jehan F, Neveu I, Barbot N, Binderup L, Brachet P, Wion D: MC903, an analogue of 1,25-dihydroxyvitamin D3, increases the synthesis of nerve growth factor. Eur J Pharmacol 1991;208:189–191.

    External Resources

  10. Saporito MS, Brown ER, Kristin CH, Wilcox HM, Vaught JL, Carswell S: Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA and protein in L929 fibroblasts and in adult rat brain. Brain Res 1994;633:189–196.
  11. Neveu I, Naveilhan P, Jehan F, Baudet C, Wion D, DeLuca HF, Brachet P: 1,25-Dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells. Mol Brain Res 1994;24:70–76.
  12. Veenstra TD, Londowski JM, Windebank AJ, Brimijoin S, Kumar R: Effects of 1,25-dihydroxyvitamin D3 on growth of mouse neuroblastoma cells. Dev Brain Res 1997;99:53–60.

    External Resources

  13. Musiol IM, Feldman D: 1,25-Dihydroxyvitamin D3 induction of nerve growth factor in L929 mouse fibroblasts: Effect of vitamin D receptor regulation and potency of vitamin D3 analogs. Endocrinology 1997;138:12–18.
  14. Matsunaga T, Yamamoto M, Mimura H, Ohta T, Kiyoki M, Ohba T, Naruchi T, Hosoi J, Kuroki T: 1,24(R)dihydroxyvitamin D3 with high activity for inducing epidermal differentiation but decreased hypercalcemic activity. J Dermatol 1990;17:135–142.
  15. Gerristen MJP, Boezeman JBM, van Vlijmen-Willems IMJJ, van de Kerkhof PCM: The effects of tacalcitol (1,24(OH)2D3) on cutaneous inflammation, epidermal proliferation and keratinization in psoriasis: A placebo-controlled, double-blind study. Br J Dermatol 1994;131:57–63.
  16. van de Kerkhof PCM, Werfel T, Haustein UF, Luger T, Czarnetzki BM, Niemann R, Planitz-Stenzel V: Tacalcitol ointment in the treatment of psoriasis vulgaris: A multicentre, placebo-controlled, double- blind study on efficacy and safety. Br J Dermatol 1996;135:758–765.
  17. Matsumoto K, Hashimoto K, Kiyoki M, Yamamoto M, Yoshikawa K: Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes. J Dermatol 1990;17:97–103.
  18. Kanzaki T, Eto H, Maeda T, Iwase H, Ito M: Morphological, biological, and biochemical characteristics of a benign human trichilemmoma cell line in vivo and in vitro. Cancer Res 1981;41:2468–2475.

    External Resources

  19. Nishioka K, Funato T, Sato Y, Ohta Y, Eto H, Katayama I, Nishiyama S: Production of interleukin 1α by a trichilemmoma cell line. J Dermatol 1990;17:205–210.
  20. Lorigados L, Soderstrom S, Ebendal T: Two-site enzyme immunoassay for β NGF applied to human patient sera. J Neurosci Res 1992;32:329–339.
  21. Neveu I, Naveilhan P, Baudet C, Brachet P, Metsis M: 1,25-Dihydroxyvitamin D3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 1994;6:124–126.

    External Resources

  22. Stumpf WE, Sar M, Clark SA, Deluka HF: Brain target sites for 1,25-dihydroxyvitamin D3. Science 1982;215:1403–1405.

    External Resources

  23. Clemens T, Garrett KP, Zhou XY, Pike JW, Hassler MR, Dempster DW: Immunocytochemical localization of the 1,25-dihydroxyvitamin D3 receptor in target cells. Endocrinology 1988;122:1224–1230.
  24. Sutherland MK, Somerville MJ, Yoong LKK, Bergeron C, Haussler MR, Crapper DR, McLachlan C: Reduction of vitamin-D hormone receptor mRNA levels in Alzheimer as compared to Huntington hippocampus: Correlation with calbindin-28K mRNA levels. Mol Brain Res 1992;13:239–250.
  25. Saporito MS, Wilcox HM, Hartpence KC, Lewis ME, Vaught JL, Carswell S: Pharmacological induction of nerve growth factor mRNA in adult rat brain. Exp Neurol 1993;123:295–302.
  26. Sonnenberg J, Luine VN, Krey LC, Christakos S: 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 1986;118:1433–1439.
  27. Carswell S: Vitamin D in the nervous system: Actions and therapeutic potential; in Feldman D, Glorieux FH, Pike JW (eds): Vitamin D. San Diego, Academic Press, 1988, pp 1197–1211.
  28. Katayama I, Miyazaki Y, Nishioka K: Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo. Br J Dermatol 1996;135:237–240.
  29. Wong SS, Goh CL: Double-blind, right/left comparison of calcipotriol ointment and betamethasone ointment in the treatment of prurigo nodularis. Arch Dermatol 2000;136:807–808.
  30. Veenstra TD, Fahnestock M, Kumar R: An AP-1 site in the nerve growth factor promoter is essential for 1,25-dihydroxyvitamin D3-mediated nerve growth factor expression in osteoblasts. Biochemistry 1998;37:5988–5994.

    External Resources

  31. Kato T, Rokugo M, Terui T, Tagami H: Successful treatment of psoriasis with topical application of active vitamin D3 analogue, 1,24-dihydroxycholecalciferol. Br J Dermatol 1986;115:431–433.

    External Resources

  32. Ohta T, Okabe K, Azuma Y, Kiyoki M: In vivo microautoradiography of [3H]1,24(OH)2D3 (tacalcitol) following topical application to normal rats and in vitro metabolism in human keratinocytes. Arch Dermatol Res 1996;288:188–196.
  33. Ohta T, Takada Y, Mimura H, Yamamoto M, Matsunaga T, Kiyoki M, Ohba T, Naruchi T: Pharmacokinetic studies of 1α,24(R)-(OH)2D3 (TV-02) (1): Plasma level, distribution, metabolism and excretion after single subcutaneous administration to rats. Xenobiot Metab Dispos 1990;5:3–23.
  34. Ishizuka S, Honda A, Mori Y, Kurihara Tatsumi J, Anai K, Ikeda K: Effects of vitamin D binding proteins on biological function of 1α,25-dihydroxyvitamin D3 analogues; in Norman AW, Bouillon R, Thomassete M (eds): Vitamin D – a pluripotent steroid hormone: Structural studies, molecular endocrinology and clinical applications. Berlin, de Gruyter, 1994, pp 109–110.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50