TY - JOUR
T1 - Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes
T2 - Possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease
AU - Kamijo, M.
AU - Nishiyama, C.
AU - Takagi, A.
AU - Nakano, N.
AU - Hara, M.
AU - Ikeda, S.
AU - Okumura, K.
AU - Ogawa, H.
PY - 2012/5
Y1 - 2012/5
N2 - Background ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca 2+-ATPase2 (SERCA2) is a Darier disease (DD)-related gene. Ultraviolet (UV) B irradiation downregulates ATP2A2/SERCA2 expression in keratinocytes, whereas cyclooxygenase-2 (COX-2) expression is dramatically upregulated by UVB. Objectives To analyse the involvement of COX-2 in ATP2A2/SERCA2 expression. Methods Keratinocytes were transfected with COX-2 siRNA or treated with COX-2 inhibitor, celecoxib, to evaluate the effect of COX-2 on ATP2A2/SERCA2 expression. Quantitative real-time polymerase chain reaction, Western blotting analysis and reporter assay were used to determine the amount of mRNA, protein level and transcription activity, respectively. Results COX-2 knockdown by siRNA resulted in upregulation of ATP2A2 transcription. Treatment by celecoxib rescued UVB-mediated suppression of the ATP2A2 transcription and SERCA2 protein expression. Simple addition of prostaglandin (PG) E 2, which is a product of COX-2 enzyme, reduced the amounts of ATP2A2 mRNA and SERCA2 protein in keratinocytes. Conclusions UVB downregulates ATP2A2/SERCA2 expression via induction of COX-2 expression and subsequent increase of PGE 2 production in keratinocytes. Considering that DD is caused by the decreased function of SERCA2 due to the reduced expression of the ATP2A2 gene, this finding shows the possibility that COX-2 inhibition may be useful to prevent and/or treat DD.
AB - Background ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca 2+-ATPase2 (SERCA2) is a Darier disease (DD)-related gene. Ultraviolet (UV) B irradiation downregulates ATP2A2/SERCA2 expression in keratinocytes, whereas cyclooxygenase-2 (COX-2) expression is dramatically upregulated by UVB. Objectives To analyse the involvement of COX-2 in ATP2A2/SERCA2 expression. Methods Keratinocytes were transfected with COX-2 siRNA or treated with COX-2 inhibitor, celecoxib, to evaluate the effect of COX-2 on ATP2A2/SERCA2 expression. Quantitative real-time polymerase chain reaction, Western blotting analysis and reporter assay were used to determine the amount of mRNA, protein level and transcription activity, respectively. Results COX-2 knockdown by siRNA resulted in upregulation of ATP2A2 transcription. Treatment by celecoxib rescued UVB-mediated suppression of the ATP2A2 transcription and SERCA2 protein expression. Simple addition of prostaglandin (PG) E 2, which is a product of COX-2 enzyme, reduced the amounts of ATP2A2 mRNA and SERCA2 protein in keratinocytes. Conclusions UVB downregulates ATP2A2/SERCA2 expression via induction of COX-2 expression and subsequent increase of PGE 2 production in keratinocytes. Considering that DD is caused by the decreased function of SERCA2 due to the reduced expression of the ATP2A2 gene, this finding shows the possibility that COX-2 inhibition may be useful to prevent and/or treat DD.
UR - http://www.scopus.com/inward/record.url?scp=84860330559&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2133.2011.10789.x
DO - 10.1111/j.1365-2133.2011.10789.x
M3 - Article
C2 - 22413864
AN - SCOPUS:84860330559
SN - 0007-0963
VL - 166
SP - 1017
EP - 1022
JO - British Journal of Dermatology
JF - British Journal of Dermatology
IS - 5
ER -