72-kD heat shock protein is a mediator of resistance to ultraviolet B light.
We have shown previously that human epidermal keratinocytes in situ and in vitro constitutively express high levels of the 72-kD heat shock protein (hsp72) and that hsp72 expression in these cells can be further induced with heat treatment. In the present study, we continue our investigation of the ultraviolet (UV) B protective effect of hyperthermic treatment and ask whether hsp72 is a mediator of heat-shock-induced UVB resistance. The results of our experiments demonstrate that heat treatment (42 degrees C for 4 h) before UVB exposure is able to increase significantly the UVB resistance of the epidermal carcinoma cell line A431. Heat-induced UVB resistance was most pronounced if the cells were exposed to UVB immediately after heat treatment. The protective effect was not detectable beyond a recovery period of 12 h. To investigate the role of hsp72 in hyperthermia-induced UVB resistance, we inhibited the expression of this protein using either a specific antisense oligodeoxynucleotide or quercetin, a flavonoid that has been shown to down-regulate hsp expression. Treatment with the oligomer as well as with quercetin significantly increased the susceptibility of A431 to UVB-induced damage and nullified the protective effect of heat preconditioning. A noncomplementary control oligodeoxynucleotide had no significant effect. These results indicate that heat treatment is able to induce a state of increased resistance to the deleterious effects of UVB in human keratinocytes in vitro. hsp72 is a molecular mediator of this protective effect, and its constitutive expression in human epidermal keratinocytes may be an important mechanism for the protection of human epidermis from UVB-induced damage.
Trautinger
F
F
Department of Dermatology, University of Vienna, Austria.
Kindås-Mügge
I
I
Barlan
B
B
Neuner
P
P
Knobler
R M
RM
D001483:Base Sequence; D002470:Cell Survival; D004817:Epidermis / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D011794:Quercetin