1,25-dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes

✍ Scribed by Petra De Haes; Marjan Garmyn; Hugo Degreef; Katleen Vantieghem; Roger Bouillon; Siegfried Segaert

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 370 KB
• Volume: 89
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10540

✦ Synopsis

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.