CONTINUING MECHANISTIC STUDIES OF UVA PHOTOIMMUNOPROTECTION

阳光中的UVB部分会导致晒伤、晒黑、皮肤癌和抑制免疫功能。波长较长的长波紫外线的破坏性要小得多，它可能会导致光老化和对更深的皮肤层的损害，但对它的研究要少得多。uvb诱导的免疫抑制似乎是皮肤癌的先决条件，免疫抑制的实验保护也降低了长期皮肤癌结果的严重程度。我们已经确定了UVA辐射对uvb免疫抑制的保护作用，当UVA以非燃烧的环境相关剂量给予小鼠时。这是一个重要的、前所未有的发现，最近对人类的观察也支持了这一发现。本研究的目的是根据两个主要假设，阐明这种对uvb诱导的免疫抑制的抗性是如何实现的。UVA干扰顺式尿酸的作用，顺式尿酸是一种天然的表皮紫外线光产物，似乎通过与组胺相互作用而启动免疫抑制。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，它们对抗uvb免疫抑制的明显氧化需求。这些途径导致预测，增加UVA成分的入射辐射将减少皮肤癌的发展。人类通常会通过uvb防晒霜或在化妆品日光浴厅接受不成比例的大剂量UVA。UVA导致UVB皮肤损伤的假设在中等剂量的紫外线下可能不成立，UVA可能保护免受UVB抑制的免疫和皮肤癌的风险，这表明广谱防晒霜是禁忌的，需要利用UVA的作用。

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.