Human skin is exposed to infrared radiation (IR) from natural and artificial sources. In previous studies, near IR radiation (IRA; 760-1,440 nm) was shown to elicit a retrograde mitochondrial signaling response leading to induction of matrix metalloproteinase-1 (MMP-1) expression. These studies, however, have exclusively employed cultured human skin fibroblasts ex vivo. Here, we have assessed the in vivo relevance of these observations by exposing healthy human skin in vivo to physiologically relevant doses of IRA. Eighty percent of the tested individuals responded to IRA radiation by upregulating of MMP-1 expression. Specifically, IRA irradiation caused increased expression of MMP-1 in the dermis, but not in the epidermis. Raman spectroscopy revealed that IRA radiation also caused a significant decrease in the antioxidant content of human skin. In vitro studies had previously shown that IRA-induced MMP-1 expression was mediated through an oxidative stress response, which originates from the mitochondrial electron transport chain. We now report that incubation of cultured human dermal fibroblasts or treatment of human skin with specific antioxidants prevented IRA radiation-induced MMP-1 expression in vitro and in vivo. Thus, IRA irradiation most likely promotes premature skin aging and topical application of appropriate antioxidants represents an effective photoprotective strategy.

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Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

Ultraviolet-B (UVB) (290 -320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiationinduced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40 -45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.