Conflicts of interest: None declared
Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1
Article first published online: 10 MAR 2005
British Journal of Dermatology
Volume 152, Issue 4, pages 697–701, April 2005
How to Cite
Mayuzumi, N., Ikeda, S., Kawada, H., Fan, P.S. and Ogawa, H. (2005), Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. British Journal of Dermatology, 152: 697–701. doi: 10.1111/j.1365-2133.2005.06383.x
- Issue published online: 11 APR 2005
- Article first published online: 10 MAR 2005
- Accepted for publication 17 August 2004
- Darier disease;
- gene expression;
- Hailey–Hailey disease;
- ultraviolet B
Summary Background Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases.
Objectives To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation.
Methods The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1·8 mmol L−1 as opposed to 0·08 mmol L−1 Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction.
Results Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration.
Conclusions The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.