Calcineurin activity and inhibition in skin and (epi)dermal cell cultures

The Journal of Investigative Dermatology
N P M SmitJ Van Pelt

Abstract

Calcineurin (Cn) is the target of the immunosuppressive drugs cyclosporine A (CsA), tacrolimus (Trl), and pimecrolimus (Prl). Trl and Prl are often used topically for treatment of various skin diseases. The Cn inhibitors CsA and Trl are mostly used for maintenance therapy of transplant patients. Their long-term use, however, causes a dramatic increase in skin cancer risk. By using a newly developed assay for Cn measurement in blood, we were able to demonstrate Cn activity in total skin homogenates. A significantly higher activity was found in epidermis compared to dermis. In skin cell cultures, fibroblasts showed the highest activity as compared to keratinocytes and melanocytes. Of the Cn inhibitors, Trl showed stronger inhibition than CsA and Prl (57 and 55% in fibroblast and keratinocyte cultures, respectively). Also, the lowest IC(50) (the half maximal inhibitory concentration) values were found for Trl (0.5 and 1.3 nM in two different fibroblast cultures). Cn activity and its inhibition can thus be studied in dermatological samples. The effects of Cn inhibition in fibroblasts and keratinocytes may be of influence on the overall functioning of the skin immune system.

References

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Citations

May 9, 2012·Mutation Research·Ruben E A MussonNico P M Smit
Jul 25, 2009·The Journal of Investigative Dermatology·Juan A PenaJennifer L Gooch
Mar 20, 2009·Genes, Chromosomes & Cancer·Amy M DworkinAmanda Ewart Toland
Nov 26, 2009·Photochemistry and Photobiology·Nico SmitJohannes van Pelt
Mar 1, 2011·Free Radical Biology & Medicine·Ruben E A MussonNico P M Smit
Oct 22, 2011·Clinical Chemistry·Ruben E A MussonNico P M Smit
Jan 1, 2016·International Journal of Oncology·Éva KatonaRóza Zákány
May 4, 2017·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Ping XuZhong-Sheng Min
Sep 19, 2018·International Journal of Molecular Medicine·Novi KusumaningrumJin Ho Chung
Apr 17, 2020·Current Pharmaceutical Biotechnology·Grażyna JanikowskaTomasz Janikowski
May 3, 2014·The Journal of Allergy and Clinical Immunology·Saakshi KhattriEmma Guttman-Yassky

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