Are suberythemal doses of ultraviolet B good for your skin?

Ultraviolet radiation B (UVB; wavelength 280–320 nm), while representing only ∼5% of the ultraviolet spectrum of the solar radiation reaching the surface of the earth, is very efficient at cutaneous biological effects (Bjorn, 2008; Slominski and Wortsman, 2000). Because of its involvement in the aetiology of epidermal cancers (basal and squamous cell carcinomas) and in melanomagenesis (Bikle, 2008), a negative health impact of UVB has been emphasized recently, especially in the pigment cell biology field. In this context, the paper by Hong et al. (2008) on the biopositive effects of UVB on the epidermis deserves special attention. The authors have clearly demonstrated that exposure of hairless mice to UVB at 40 mJ cm−2 (approximately ½ minimal erythema dose) daily for 1–3 days clearly strengthens the epidermal barrier function and stimulates antimicrobial peptide production. This indicates that suberythemal doses of UVB may have direct beneficial effects on functions of the skin as well as serving as a useful strategy in treatment of atopic dermatitis, which is in contrast to its negative effect at high doses (Hong et al., 2008). The proposed mechanism of action includes stimulation of the vitamin D3 (D3) signalling system, as UVB induces the expression of the vitamin D receptor and CYP27B1 (encoding 1α-hydroxylase) genes, and use of 1α-hydroxylase inhibitor ketoconazole attenuated these affects apparently via inhibition of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3 formation (Hong et al., 2008). The photochemical isomerization of 7-dehydrocholesterol (7DHC) after absorption of UVB photons to a pre-vitamin D3 intermediate, followed by its slow isomerization to three main products including D3, tachysterol and lumisterol, represents the most fundamental reactions in the photobiology of the skin [reviewed in Holick (2007); Bikle (2008); Bjorn (2008)] (Fig. 1). This conversion and the relative ratio of products depend on the dose of absorbed energy, temperature, wavelength, the presence of singlet oxygen, chemical milieu or of biological membranes [reviewed in Holick (2007); Bikle (2008); Bjorn (2008)]. For example, higher doses of UV can trigger further isomerization of tachysterol to isotachysterols, which is followed by autoxidation, or further degradation/isomerization of D3 with production of suprasterols I and II [reviewed in Holick (2007); Bjorn (2008)]. Also, the presence of singlet oxygen and photosensitizers can transform 7DHC to corresponding 5,7,9(11)-triene (9DDHC) (Fig. 1). Photolysis of 7-dehydrocholesterol (cholesta-5,7-diene-3β-ol; pro-vitamin D3). Vitamin D3 after entering circulation is successively hydroxylated in the liver and kidney to 1,25(OH)2D3 to regulate body calcium metabolism as well as to mediate several pleiotropic effects [reviewed in Holick (2007); Bikle (2008)], serves as an example of endocrine function of the skin (Slominski and Wortsman, 2000). 1,25(OH)2D3 is also produced in the epidermis from D3 and has significant local actions on formation of the skin barrier, and functional differentiation of adnexal structures, and modulation of the skin immune system (reviewed in Holick (2007); Bikle (2008)). These local activities are consistent with the results and conclusions of the paper by Hong et al. (2008), which challenges the current dermatological opinion that UVB is only deleterious for the skin, and that orally delivered D3 can replace all of the functions of the cutaneously formed derivatives of D3 [see variety of UVB induced transformation of pro-vitamin D3 (Fig. 1)]. Furthermore, the pharmaceutical industry is investing significant effort to develop synthetic non-calcemic vitamin D analogues that could serve as potent anticancer drugs. In the above context it is also important to mention that the skin expresses CYP11A1 (Slominski et al., 2004b), which can modify the side chain of D3 (Slominski et al., 2005) or cleave the side chain of 7DHC to produce 7-dehydropregnenolone that can further be modified by steroidogenic enzymes and such products can undergo photochemical transformation to vitamin D-like products without the side chain (Fig. 2) (Slominski et al., 2004b). Photolysis of pregna-5,7-diene-steroidal products of P450scc and other steroidogenic enzymes action on 7-dehydrocholesterol and 7-dehydropregnolone (Slominski et al., 2004b). Thus, the correct question to be asked is how much UVB is bad or good for the skin taking into consideration its level of pigmentation. This presents new and exciting experimental opportunities for pigment biologists, as skin pigmentation affects UVB-induced D3 production and D3 (and perhaps other derivatives presented in 1, 2) can affect skin pigmentation and activities of normal and malignant melanocytes [reviewed in Slominski et al. (2004a)].

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