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1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2003 Jul 01; Vol. 89 (4), pp. 663-73. - Publication Year :
- 2003
-
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 microM 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 microM diminished UVB-stimulated JNK activation with more than 30%. 1,25(OH)(2)D(3) treatment (1 microM) 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.<br /> (Copyright 2003 Wiley-Liss, Inc.)
- Subjects :
- Apoptosis radiation effects
Blotting, Northern
Blotting, Western
Cell Survival drug effects
Cell Survival radiation effects
Cytochromes c biosynthesis
Cytochromes c radiation effects
Dose-Response Relationship, Drug
Enzyme Activation drug effects
Enzyme Activation radiation effects
Enzyme-Linked Immunosorbent Assay
Humans
Interleukin-6 radiation effects
JNK Mitogen-Activated Protein Kinases
Keratinocytes cytology
Keratinocytes metabolism
Microscopy, Fluorescence
Mitogen-Activated Protein Kinases radiation effects
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha radiation effects
Ultraviolet Rays
Up-Regulation radiation effects
Apoptosis drug effects
Calcitriol pharmacology
Interleukin-6 biosynthesis
Keratinocytes drug effects
Keratinocytes radiation effects
Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 89
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12858333
- Full Text :
- https://doi.org/10.1002/jcb.10540