N Mayuzumi1, S Ikeda, H Kawada, H Ogawa. 1. Department of Dermatology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. mayu@med.juntendo.ac.jp
Abstract
BACKGROUND: Darier's disease (DD) and Hailey-Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids. OBJECTIVES: To investigate the molecular basis for DD and HHD. METHODS: We used quantitative reverse transcriptase-polymerase chain reactions to examine the effects of UVB irradiation on ATP2A2 and ATP2C1 mRNA levels in cultured normal keratinocytes. RESULTS: We observed that UVB irradiation reduced ATP2A2 and ATP2C mRNA levels. The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D(3). The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression. CONCLUSIONS: These results suggest that drugs effective for DD and HHD act by modulating ATP2A2 and ATP2C1 mRNA expression, respectively, and that the proinflammatory cytokines IL-6 and IL-8 play important roles in the regulation of ATPA2 and ATP2C1 expression in homeostasis and/or inflammation of the skin.
BACKGROUND: Darier's disease (DD) and Hailey-Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids. OBJECTIVES: To investigate the molecular basis for DD and HHD. METHODS: We used quantitative reverse transcriptase-polymerase chain reactions to examine the effects of UVB irradiation on ATP2A2 and ATP2C1 mRNA levels in cultured normal keratinocytes. RESULTS: We observed that UVB irradiation reduced ATP2A2 and ATP2C mRNA levels. The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D(3). The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression. CONCLUSIONS: These results suggest that drugs effective for DD and HHD act by modulating ATP2A2 and ATP2C1 mRNA expression, respectively, and that the proinflammatory cytokines IL-6 and IL-8 play important roles in the regulation of ATPA2 and ATP2C1 expression in homeostasis and/or inflammation of the skin.
Authors: Ryan P Hobbs; Evangeline V Amargo; Agila Somasundaram; Cory L Simpson; Murali Prakriya; Mitchell F Denning; Kathleen J Green Journal: FASEB J Date: 2010-12-14 Impact factor: 5.191
Authors: A Young Park; Ho Jung Lee; Euy Hyun Chung; Jung Eun Kim; Jong Suk Lee; Sang Hoon Lee; Sung Yul Lee Journal: Ann Dermatol Date: 2019-07-01 Impact factor: 1.444