1. Department of Pathology, Vancouver General Hospital, University of British Columbia and Skin Cancer Research Laboratory, Jack Bell Research Center, Vancouver, British Columbia, Canada
2. ^*Division of Dermatology, Vancouver General Hospital, University of British Columbia and Skin Cancer Research Laboratory, Jack Bell Research Center, Vancouver, British Columbia, Canada

Correspondence: Dr Martin J. Trotter, Department of Pathology (Anatomical Pathology), Vancouver General Hospital, 910 West 10th Avenue, Vancouver, B.C., Canada V5Z 1 L8.

Received 22 July 1997; Revised 19 March 1998; Accepted 3 April 1998.

Abstract

In response to ultraviolet radiation (UVR), skin keratinocytes increase expression of heat shock proteins that can protect cells from stress-induced damage. This heat shock response is known to be transcriptionally regulated in eukaryotic cells exposed to certain forms of environmental stress. In the skin, absorption of ultraviolet B light occurs primarily in the epidermis, and therefore, using primary cultures of normal human epidermal keratinocytes, we have examined whether transcriptional activation of the hsp72 gene occurs following UVB irradiation. Cultured keratinocytes were exposed to UVB (290–320 nm, 300 J per m²) and then incubated at 37°C for various intervals before harvesting. Immediately following UV exposure, the heat shock transcription factor 1 (HSF1) dissociated from HSP72-HSF1 complexes, underwent trimerization and phosphorylation, and demonstrated DNA binding activity to the heat shock element in the promoter region of the hsp72 gene. UVB also increased hsp72 mRNA, with peak levels observed 1–3 h post-UVR. HSP72 protein was constitutively expressed in keratinocytes, and its expression was increased by UVB, with maximum levels at 6 h post-UVR. The stress response may be extremely important in the protection of human skin from UVB radiation, and modulation of heat shock protein expression and/or function offers a potential therapeutic target in the prevention of photoaging and skin cancer.