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1,25‐dihydroxyvitamin D 3 inhibits ultraviolet B‐induced apoptosis, Jun kinase activation, and interleukin‐6 production in primary human keratinocytes
Author(s) -
De Haes Petra,
Garmyn Marjan,
Degreef Hugo,
Vantieghem Katleen,
Bouillon Roger,
Segaert Siegfried
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10540
Subject(s) - apoptosis , dna fragmentation , programmed cell death , microbiology and biotechnology , keratinocyte , kinase , chemistry , biology , biochemistry , in vitro
Abstract We investigated the capacity of 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] to protect human keratinocytes against the hazardous effects of ultraviolet B (UVB)‐irradiation, recognized as the most important etiological factor in the development of skin cancer. Cytoprotective effects of 1,25(OH) 2 D 3 on UVB‐irradiated keratinocytes were seen morphologically and quantified using a colorimetric survival assay. Moreover, 1,25(OH) 2 D 3 suppressed UVB‐induced apoptotic cell death. An ELISA, detecting DNA‐fragmentation, demonstrated that pretreatment of keratinocytes with 1,25(OH) 2 D 3 1 μM for 24 h reduced UVB‐stimulated apoptosis by 55–70%. This suppression required pharmacological concentrations 1,25(OH) 2 D 3 and a preincubation period of several hours. In addition, 1,25(OH) 2 D 3 also inhibited mitochondrial cytochrome c release (90%), a hallmark event of UVB‐induced apoptosis. Furthermore, we demonstrated that 1,25(OH) 2 D 3 reduced two important mediators of the UV‐response, namely, c‐Jun‐NH 2 ‐terminal kinase (JNK) activation and interleukin‐6 (IL‐6) production. As shown by Western blotting, pretreatment of keratinocytes with 1,25(OH) 2 D 3 1 μM diminished UVB‐stimulated JNK activation with more than 30%. 1,25(OH) 2 D 3 treatment (1 μM) reduced UVB‐induced IL‐6 mRNA expression and secretion with 75–90%. Taken together, these findings suggest the existence of a photoprotective effect of active vitamin D 3 and create new perspectives for the pharmacological use of active vitamin D compounds in the prevention of UVB‐induced skin damage and carcinogenesis. J. Cell. Biochem. 89: 663–673, 2003. © 2003 Wiley‐Liss, Inc.