Biomedical subjects

R Bestak

Publications and source records attributed to R Bestak.

5 recordsLinked to original sources

PubMed1998

UVA-induced immunosuppression.

It has previously been demonstrated that chronic low-dose solar-simulated ultraviolet (UV) radiation can induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. Epidermal cells from UV-irradiated mice inhibit spontaneous regression of tumours indicating that UV-induced immunosuppression is likely to permit the outgrowth of developing UV-induced skin tumours. We have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA + B significantly suppressed the local and systemic primary contact sensitivity (CS) response to the hapten TNCB. Furthermore UVA + B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) numbers in chronically UV-irradiated mice. UVA-irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with UVA + B or UVA radiation also induced an impaired secondary CS response, and this tolerance was transferable with spleen cells. Therefore exposure of C3H/HeJ mice 5 days per week for 4 weeks with UVA can induce local immunosuppression and tolerance. One of the mechanisms by which UVA affects biological systems is production of reactive oxygen species. We have also shown that Vitamin E, an inhibitor of lipid peroxidation, prevents UV-induced immunosuppression and loss of LC. It is possible that the UVA in UV radiation induces epidermal lipid peroxidation which stimulates LC migration from the epidermis, thus contributing to UV-induced immunosuppression. Hence, inhibition of epidermal lipid peroxidation by Vitamin E may provide some protection to the skin immune system from these effects of UV.

Animals↗

PubMed1998

Sunscreens and vitamin E provide some protection to the skin immune system from solar-simulated UV radiation.

Previous studies have indicated that sunscreens designed to protect from erythema do not adequately prevent immunosuppression. Mice were irradiated with suberythemal doses of solar-simulated ultraviolet radiation (ssUVR) to assess the immunoprotective ability of sunscreens. Whereas C3H/HeJ and BALB/c mice had similar sensitivities to ssUVR-induced inflammation, C3H/HeJ mice were more sensitive to ssUVR-induced immunosuppression. Octyl dimethyl-p-aminobenzoic acid did not protect from immunosuppression and, thus, had an immune protection factor (IPF) of 1. 2-Ethylhexyl-p-methoxycinnamate and microfine titanium dioxide provided limited protection, both having IPF values of 1.127. Immune protection by the sunscreens appeared to be dependent upon absorption of UVA as well as UVB, and was much less than predicted from the sun protection factor. Vitamin E, an inhibitor of lipid peroxidation, also protected the immune system, with an IPF of 1.2, indicating that oxidation of lipids is involved in UVR-induced immunosuppression, and that it should be possible to develop sunscreens which protect the immune system.

Animals↗

PubMed1996

Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice.

It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/ HeJ mice. Irradiation with UVA + B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore UVA + B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA + B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. These results suggest that depletion of LC, but not DETC, may be involved in UVA-induced local immunosuppression in our model, and that tolerance was induced in the presence of normal numbers of DETC. Hence exposure of C3H/HeJ mice 5 days per week for 4 weeks with UVA can induce local immunosuppression and tolerance.

Animals↗

PubMed1996

Sunscreens protect from UV-promoted squamous cell carcinoma in mice chronically irradiated with doses of UV radiation insufficient to cause edema.

Previously we reported that the broad-spectrum sunscreen microfine titanium dioxide (MTD) could completely protect C3H/HeJ mice from UV radiation-induced immunosuppression to a contact sensitizer. In contrast, 2-ethylhexyl p-methoxycinnamate (2-EHMC), a UVB-absorbing sunscreen, only partially protected the skin immune system. In this study we investigated further this differential protection of the skin immune system by comparing the ability of 2-EHMC and MTD to protect these mice from the promotion phase of tumorigenesis. The mice were initiated using a single subcarcinogenic dose of 7,12-dimethylbenz(alpha)anthracene (DMBA) followed by promotion with chronic low-dose solar-simulated UV radiation for 32 weeks. We used doses of UV insufficient to cause edema in order to simulate daily human exposure to solar UV radiation. Mice were observed for the appearance of squamous cell carcinomas for 48 weeks. The DMBA-initiation alone and DMBA-initiated, sunscreen-treated groups did not develop tumors. Ultra-violet alone induced the appearance of tumors in 46% of mice at week 48 and therefore some tumors were initiated by UV. Initiation with DMBA prior to UV irradiation enhanced tumorigenesis such that 87% of mice at week 48 had tumors. Both 2-EHMC and MTD completely protected these mice from UV-induced promotion as well as from complete carcinogenesis despite the different UV-absorption spectra of the sunscreens and their differential abilities to protect from UV-induced immuno-suppression. Furthermore, we have shown that, if UV exposure is not increased to compensate for tolerance to edema, protection from tumorigenesis is afforded by sunscreens.

Animals↗

PubMed1995

Sunscreen protection of contact hypersensitivity responses from chronic solar-simulated ultraviolet irradiation correlates with the absorption spectrum of the sunscreen.

This study compares the ability of two ultraviolet (UV) B-absorbing sunscreens, 2-ethylhexyl p-methoxycinnamate (2-EHMC) and 2-ethylhexyl p-aminobenzoate (Padimate O), and two physical sunscreens, microfine titanium dioxide (MTD) and zinc oxide, to protect the skin immune system from chronic (4 weeks) solar-simulated UV irradiation. Mice were exposed to suberythemal doses of UV before assessing local and systemic immunosuppression and tolerance to a contact sensitizer. Using a UV protocol that induced local but not systemic immunosuppression or tolerance in BALB/c mice, it was shown that Padimate O made the immunosuppression worse, whereas 2-EHMC and MTD protected the immune system. When the cumulative dose was increased by 12.7%, causing systemic immunosuppression and tolerance, none of the sunscreens protected from immunosuppression, but 2-EHMC provided partial, and MTD gave complete protection from tolerance. To examine this apparent lack of protection from systemic immunosuppression, C3H/HeJ mice were used. These mice had a minimal erythema dose similar to that of the BALB/c mice but were systemically immunosuppressed, with only 44% of the UV dose required to immunosuppress BALB/c mice. 2-EHMC provided some protection, whereas MTD provided complete protection from systemic immunosuppression in C3H/HeJ mice. Hence, sunscreens can protect from local and systemic immunosuppression, although this protection is limited and is not related to the sun protection factor of the sunscreens or the minimal erythema dose of the mouse strain. Instead, protection seems to be related to the sunscreens' having a broad absorption spectrum.

4-Aminobenzoic Acid↗