Skip to main content

Advertisement

Log in

Cyclosporin A-induced hair growth in mice is associated with inhibition of hair follicle regression

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

Abstract

Background

Cyclosporin A (CsA) often causes hair growth in transplant recipients. Our objectives were to evaluate the effect of CsA on follicular hair keratinocyte growth in nude mice by assessing their proliferation in vivo, and to assess the ability of CsA to prevent follicular keratinocyte apoptosis in vivo and chemotherapy-induced keratinocyte apoptosis in vitro.

Methods

Nude mice were fed various daily doses of CsA (10–100 mg/kg). Dorsal skin sections stained with hematoxylin and eosin, followed by immunostaining with 4-deoxybromouridine, were examined for determination of hair follicle number and hair follicle keratinocyte proliferation. Follicular keratinocytes were isolated and examined for apoptotic status. Apoptosis was induced in vitro in a keratinocyte cell line by 4-hydroperoxycyclophosphamide. The antiapoptotic effects of various CsA concentrations (0.1–5 μg/ml) were measured by annexin-V/propidium iodide binding.

Results

CsA caused a dose-dependent increase in the number of hair follicles but had no effect on follicular keratinocyte proliferation. Treatment with CsA decreased the number of apoptotic follicular keratinocytes. In vitro, there was a dose-dependent inhibition of the extent of early and late apoptosis of treated keratinocytes.

Conclusion

CsA may induce hair growth by increasing the number of hair follicles and inhibiting apoptosis of follicular keratinocytes, thereby delaying hair follicle regression.

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.

Fig. 1a, b
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kahan BD, Flechner SM, Lorber MI, Golden D, Conley S, Van Buren CT (1989) Complications of cyclosporin-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center from one to five years. Transplantation 43:197–204

    Google Scholar 

  2. Paus R, Stenn KS, Link RE (1989) The induction of anagen hair growth in mouse skin by cyclosporine A administration. Lab Invest 60:365–369

    CAS  PubMed  Google Scholar 

  3. Jiang H, Yamamoto S, Kato R (1995) Induction of anagen in telogen mouse skin by topical application of FK506, a potent immunosuppressant. J Invest Dermatol 104:523–525

    Article  CAS  PubMed  Google Scholar 

  4. Maurer M, Handjiski B, Paus R (1997) Hair growth modulation by topical immunophilin ligands. Induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am J Pathol 150:1433–1441

    CAS  PubMed  Google Scholar 

  5. Paus R, Handjiski B, Czarnetzki BM, Eichmuller S (1999) A murine model for inducing and manipulating hair follicle regression (catagen): effects of dexamethasone and cyclosporin A. J Invest Dermatol 4:338–345

    CAS  Google Scholar 

  6. Yamamoto S, Jiang H, Kato RJ (1994) Stimulation of hair growth by topical application of FK506, a potent immunosuppressive agent. J Invest Dermatol 102:160–164

    Article  CAS  PubMed  Google Scholar 

  7. Flanagan S (1966) “Nude”, a new hairless gene with pleiotropic effects in the mouse. Genet Res 8:295–309

    CAS  PubMed  Google Scholar 

  8. Pantelouris EM (1973) Athymic development in the mouse. Differentiation 1:437–450

    CAS  PubMed  Google Scholar 

  9. Gafter-Gvili A, Sredni B, Gal R, Gafter U, Kalechman Y (2003) Cyclosporin A-induced hair growth in mouse is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes. Am J Physiol Cell Physiol 284:1593–1603

    Google Scholar 

  10. Margerl M (1998) Patterns of proliferation and apoptosis during hair follicle morphogenesis. J Invest Dermatol 110:532a

    Google Scholar 

  11. Lindner G, Botchkarev VA, Botchkarev NV, Ling G, Van der Veen C, Paus R (1997) Analysis of apoptosis during murine hair follicle regression. Am J Pathol 151:1601–1617

    CAS  PubMed  Google Scholar 

  12. Paus R, Bottge JA, Henz BM, Maurer M (1996) Hair growth control by immunosuppression. Arch Dermatol Res 288:408–410

    Article  CAS  PubMed  Google Scholar 

  13. Tanigaki N, Ando H, Ito M, Hashimoto A, Kitano Y (1990) Electron microscopic study of cultured cells from the murine hair tissues: cell growth and differentiation. Arch Dermatol Res 282:402–407

    CAS  PubMed  Google Scholar 

  14. Kalechman Y, Strassmann G, Albeck M, Sredni B (1998) Up-regulation by ammonium trichloro(dioxyethlene-0,0′)tellurate (AS101) of Fas/Apo-1 expression on B16 melanoma cells: implications for the anti-tumor effects of AS101. J Immunol 161:3536–3543

    CAS  PubMed  Google Scholar 

  15. Kawa Y, Takahashi H (1991) Hair growth on nude mice due to cyclosporin A. J Dermatol 18:714–719

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Uzi Gafter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gafter-Gvili, A., Kalechman, Y., Sredni, B. et al. Cyclosporin A-induced hair growth in mice is associated with inhibition of hair follicle regression. Arch Dermatol Res 296, 265–269 (2004). https://doi.org/10.1007/s00403-004-0516-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-004-0516-x

Keywords

Navigation