High ultraviolet A protection affords greater immune protection confirming that ultraviolet A contributes to photoimmunosuppression in humans.

Solar radiation causes immunosuppression that contributes to skin cancer growth. Photoprotective strategies initially focused on the more erythemogenic ultraviolet B. More recently, the relationship of ultraviolet A and skin cancer has received increased attention. We hypothesized that if ultraviolet A contributes significantly to human ultraviolet-induced immune suppression, then increased ultraviolet A filtration by a sunscreen would better protect the immune system during ultraviolet exposure. Two hundred and eleven volunteers were randomized into study groups and received solar-simulated radiation, ranging from 0 to 2 minimum erythema dose, on gluteal skin, with or without sunscreen, 48 h prior to sensitization with dinitrochlorobenzene. Contact hypersensitivity response was evaluated by measuring the increase in skin fold thickness of five graded dinitrochlorobenzene challenge sites on the arm, 2 wk after sensitization. Clinical scoring using the North American Contact Dermatitis Group method was also performed. Solar-simulated radiation dose-response curves were generated and immune protection factor was calculated using a nonlinear regression model. Significance of immune protection between study groups was determined with the Mann-Whitney-Wilcoxon exact test. The sunscreen with high ultraviolet A absorption (ultraviolet A protection factor of 10, based on the in vivo persistent pigment darkening method) and a labeled sun protection factor of 15 demonstrated better immune protection than the product that had a low ultraviolet A absorption (ultraviolet A protection factor of 2) and a labeled sun protection factor of 15. Nonlinear regression analysis based on skin fold thickness increase revealed that the high ultraviolet A protection factor sunscreen had an immune protection factor of 50, more than three times its sun protection factor, whereas the low ultraviolet A protection factor sunscreen had an immune protection factor of 15, which was equal to its labeled sun protection factor. This study demonstrates that ultraviolet A contributes greatly to human immune suppression and that a broad-spectrum sunscreen with high ultraviolet A filtering capacity results in immune protection that exceeds erythema protection. These results show that high ultraviolet A protection is required to protect against ultraviolet-induced damage to cutaneous immunity.

Modulation of gene expression induced in human epidermis by environmental stress in vivo.

Environmental insults on the skin induce biologic responses through the modulation of expression of genes implicated in different cell functions. The aim of this study was to investigate the modulation of gene expression profile in human epidermis in vivo following different stresses. We determined the modulations of gene expression using cDNA macroarray in the epidermis of 28 healthy volunteers, following mild and physiologic insults, including: (1), tape stripping; (2) application of 10% sodium dodecyl sulfate; (3) daily application of vaseline; and (4), exposure to one minimal erythema dose of solar-simulated radiation. The analysis was performed 19 h after treatment. The reverse transcription-polymerase chain reaction method was used to confirm our results. We showed that: (1) the intensity of gene modulation was variable among the volunteers following the same skin stress; (2) the nature and intensity of skin treatment modified the pattern of gene expression; and (3) some genes were modulated only by specific stress, some others are modulated irrespective of the stress. GADD45, Bax, SAS, and granulocyte chemotactic protein-2 were overexpressed exclusively following solar-simulated radiation, whereas tape stripping led to the modulation of genes implicated in different pathways (inflammation, cell proliferation, cell differentiation, detoxification, etc.). Concerning common gene modulation, MRP8 and MRP14 were highly upregulated in human skin epidermis after solar-simulated radiation, vaseline application or tape stripping, and to a lower extent after sodium dodecyl sulfate. Such upregulation of the MRP 8/14 genes was confirmed at the protein level in an ex-vivo skin culture model following tape stripping and solar-simulated radiation. Together, these results suggest that MRP8 and MRP14 may be general, yet highly sensitive, markers for a great variety of skin stresses and that they are implicated in several epidermal repair pathways.

Biological effects of simulated ultraviolet daylight: a new approach to investigate daily photoprotection.

BACKGROUND: The irradiance of standard ultraviolet daylight (UV-DL) is representative of most frequently encountered UV exposure conditions and simulators of UV-DL can now be used to properly investigate the biological effects of a non-extreme UV radiation. One of the characteristics of the simulated UV-DL used in this study is its dUVA to dUVB irradiance ratio, which amounts to 24, instead of close to 10, for the simulated zenithal UV radiation (UV-SSR). PURPOSE/METHODS: The aim of our study was to compare photobiological effects induced, in human skin, by acute and semi-chronic exposure to simulated UV-DL with those induced by UV-SSR. RESULTS: Differences between UV doses needed to induce given biological effects after exposure to simulated UV-DL compared with UV-SSR indicate that the spectral distribution of the UV spectrum is of primary importance with regard to biological endpoints in the epidermis (SBC, p53, thymine dimers, Langerhans cells, and melanocyte alterations, etc.) and in the dermis (collagen, tenascin, etc.). Significant biological damage was noticed after 19 cumulative exposures to 0.5 minimum erythemal dose (MED) of UV-DL over 4 weeks. 0.5 MED of UV-DL corresponds to 1/9 of the daily typical dose received in Paris in April, emphasizing the need for an efficient daily UV protection. CONCLUSION: Simulated UV daylight is a relevant new tool for daily photoprotection studies.