CONTINUING MECHANISTIC STUDIES OF UVA PHOTOIMMUNOPROTECTION

阳光中的UVB部分会导致晒伤，晒黑，皮肤癌，并抑制免疫功能。较长波长的UVA损伤明显较小，可能会导致光老化和对深层皮肤的损伤，但研究较少。UVB诱导的免疫抑制似乎是皮肤癌的先决条件，实验性的免疫抑制保护也会降低长期皮肤癌的严重程度。我们已经确定了UVA辐射对UVB免疫抑制的保护作用时，UVA是在非燃烧环境相关剂量的小鼠。这是一个重要的和前所未有的发现，并得到了最近对人类的观察的支持。本研究的目的是阐明这种抵抗UVB诱导的免疫抑制的机制，根据2个主要假设：1。UVA干扰顺式尿刊酸的作用，顺式尿刊酸是一种天然的表皮UV光产物，似乎通过与组胺相互作用来启动免疫抑制。2. UVA改变免疫控制的平衡，从而激活皮肤的正常抗氧化防御，如金属硫蛋白和血红素加氧酶，其拮抗UVB免疫抑制的表观氧化需求。这些途径导致预测增加入射辐射的UVA成分将减少皮肤癌的发展。人类通常通过UVB防晒霜或在化妆品日光浴室中接受不成比例的大UVA剂量。UVA有助于UVB皮肤损伤的假设在中等UV剂量下可能不正确，并且UVA保护免受UVB抑制的免疫力和皮肤癌风险的潜力表明广谱防晒霜是禁忌的，并且需要利用UVA效应。

The UVB portion of sunlight causes sunburn, tanning, skin cancer, and suppresses immune function. Longer wavelength UVA is significantly less damaging, may contribute to photoageing and damage to deeper skin layers, but has been much less well studied. UVB-induced immunosuppression appears to be a prerequisite for skin cancer, and experimental protection from the immunosuppression results also in reduced severity of the long-term skin cancer outcome. We have identified a protective effect by UVA radiation against UVB-immunosuppression when UVA is administered to mice at non-burning environmentally relevant doses. This was an important and unprecedented finding, and is supported by recent observations also in humans. The aim of the present study is to clarify the mechanisms by which this resistance to UVB-induced immunosuppression is achieved, according to 2 main hypotheses: 1. UVA interferes with the actions of cis-urocanic acid, a natural epidermal UV-photoproduct that appears to initiate the immunosuppression by interacting with histamine. 2. UVA alters the balance of immunological control and thus activates normal antioxidant defences of the skin such as metallothionein and haem oxygenase, which antagonise the apparent oxidative requirement for UVB-immunosuppression. These pathways lead to the prediction that increasing the UVA component of the incident radiation will reduce skin cancer development. Humans typically receive disproportionately large UVA doses sunbathing through a UVB-sunscreen, or in cosmetic sunparlours. The assumption that UVA contributes to UVB skin damage may not be true at moderate UV doses, and a potential for UVA to protect from UVB-suppressed immunity and risk of skin cancer would suggest that broad spectrum sunscreens are contraindicated, and that the UVA effects need to be exploited.