Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1

Autor: Nobuyasu Mayuzumi, Hideoki Ogawa, P.S. Fan, Shigaku Ikeda, Hiroshi Kawada
Rok vydání: 2005
Předmět:
Zdroj: British Journal of Dermatology. 152:697-701
ISSN: 1365-2133
0007-0963
DOI: 10.1111/j.1365-2133.2005.06383.x
Popis: 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 (1AE8 mmol L )1 as opposed to 0AE08 mmol L )1 Ca 2+ )o nATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcriptionpolymerase 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 Ca 2+ 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.
Databáze: OpenAIRE