Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo

BMC Dermatology

Research Article

Anthony David¹  Sandrine Kurdykowski¹  Pascal Descargues¹  Leslie Calapre²  Elin S. Gray²  Mel Ziman³  Prue Hart⁴ 

[1] GENOSKIN Centre Pierre Potier, Oncopole, Toulouse, France;School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Perth, WA, Australia;School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Perth, WA, Australia;Department of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia;Telethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, 6008, Perth, Australia;

关键词: Heat stress;    UVB;    Keratinocytes;    Apoptosis;    p53;    DNA damage;   

DOI  :  10.1186/s12895-016-0043-4

 received in 2015-10-16, accepted in 2016-05-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundUV radiation induces significant DNA damage in keratinocytes and is a known risk factor for skin carcinogenesis. However, it has been reported previously that repeated and simultaneous exposure to UV and heat stress increases the rate of cutaneous tumour formation in mice. Since constant exposure to high temperatures and UV are often experienced in the environment, the effects of exposure to UV and heat needs to be clearly addressed in human epidermal cells.MethodsIn this study, we determined the effects of repeated UVB exposure 1 kJ/m2 followed by heat (39 °C) to human keratinocytes. Normal human ex vivo skin models and primary keratinocytes (NHEK) were exposed once a day to UVB and/or heat stress for four consecutive days. Cells were then assessed for changes in proliferation, apoptosis and gene expression at 2 days post-exposure, to determine the cumulative and persistent effects of UV and/or heat in skin keratinocytes.ResultsUsing ex vivo skin models and primary keratinocytes in vitro, we showed that UVB plus heat treated keratinocytes exhibit persistent DNA damage, as observed with UVB alone. However, we found that apoptosis was significantly reduced in UVB plus heat treated samples. Immunohistochemical and whole genome transcription analysis showed that multiple UVB plus heat exposures induced inactivation of the p53-mediated stress response. Furthermore, we demonstrated that repeated exposure to UV plus heat induced SIRT1 expression and a decrease in acetylated p53 in keratinocytes, which is consistent with the significant downregulation of p53-regulated pro-apoptotic and DNA damage repair genes in these cells.ConclusionOur results suggest that UVB-induced p53-mediated cell cycle arrest and apoptosis are reduced in the presence of heat stress, leading to increased survival of DNA damaged cells. Thus, exposure to UVB and heat stress may act synergistically to allow survival of damaged cells, which could have implications for initiation skin carcinogenesis.

【 授权许可】

CC BY   
© The Author(s). 2016