紫外线对人皮肤成纤维细胞的影响

紫外线辐射可造成皮肤损伤,引起皮肤出现红斑、光老化等。紫外线作用于成纤维细胞,引起细胞因子分泌及基因表达的改变,不仅能造成真皮层的损伤,还可被用来治疗某些疾病,如局限性硬皮病。从紫外线对皮肤成纤维细胞的损伤、成纤维细胞对紫外线的防御反应及紫外线的应用等方面阐述了紫外线对成纤维细胞的影响。     

皮肤DNA光损伤及其生物学后果

已经证实日光紫外线辐射可以损伤皮肤细胞DNA.中波紫外线(UVB)主要通过被表皮细胞成分如蛋白和DNA直接吸收诱导基因突变,而长波紫外线(UVA)则是通过激活内源性光敏剂局部形成氧化压力发挥基因毒性作用.欧莱雅研究院Marrot博士等综述了DNA光损伤类型及其生物学后果.     

中波紫外线诱导皮肤角质形成细胞凋亡机制的研究进展

紫外线照射表皮后引起DNA损伤的表皮细胞通过日晒伤细胞(凋亡的角质形成细胞)的形成来清除。p53、Fas、Trp53等基因的表达促进角质形成细胞凋亡,而survivin的表达则抑制角质形成细胞凋亡。紫外线照射后皮肤可产生环丁烷嘧啶二聚体和6-4光产物,这两种光产物可以作为UVB诱导凋亡的起始信号。凋亡在清除DNA损伤的皮肤起着重要作用。在皮肤中通过凋亡清除DNA损伤的细胞,防止日光诱导癌变,而不是依赖于DNA损伤的校正修复。silibinin对中波紫外线引起人HaCaT永生化角质形成细胞凋亡具有双向调控作用。对UVB引起角质形成细胞凋亡的调控药物,值得进一步研究。     

紫外线辐射诱导角质形成细胞凋亡的机制

紫外线辐射诱导角质形成细胞凋亡,与多种皮肤病理过程关系密切,已引起人们关注。紫外线可通过诱导活性氧及细胞因子产生DNA损伤和基因表达改变等致角质形成细胞凋亡,此过程有多个信号转导途径参与,其中p53、CD95、Bcl-2、半胱天冬酶、丝裂原活化蛋白激酶介导的信号转导途径起重要作用。     

紫外线照射对表皮通透屏障功能的影响及其意义

紫外线照射是影响皮肤生物功能最常见的因素之一.大部分皮肤鳞状细胞癌和基底细胞癌发生在曝光部位[1];皮肤弹性降低、皱纹增多也是常见的紫外线导致的损伤[2].皮肤色素增多、炎症形成及晒伤等也是与紫外线照射有关的皮肤病.此外,紫外线照射对表皮通透屏障功能也有不同程度的影响.然而,在防治紫外线照射对皮肤的损伤过程中,改善表皮通透屏障功能常常被忽略.为此,本文仅就紫外线照射对表皮通透屏障功能的影响及意义做一简述.     

人角质形成细胞在皮肤光老化中的研究进展

光老化是长期紫外线照射导致的慢性炎性损伤,其中长波紫外线和中波紫外线红外线可诱导皮肤损伤引起光老化,但其发病机制尚未完全明确.人角质形成细胞是表皮中重要的细胞,也是紫外线敏感的靶细胞.近年来研究表明,人角质形成细胞在光老化的发生和发展中起重要作用.其中衰老自由基学说最为热门,抗老化的机制和药物、植物等方面的研究也多从此方面入手.     

异丙嗪抑制中波紫外线辐射诱导HaCaT细胞产生白介素6

紫外线过量辐射是导致人类皮肤损伤的重要原因之一。角质形成细胞受到紫外线等外来因素刺激时,包括白介素6(IL-6)等多种细胞因子的分泌量增加^[1]。有研究证实组织胺可显著放大角质形成细胞对IL-6的基础分泌和紫外线辐射诱导的分泌^[2],而异丙嗪是一种H1受体阻滞剂,通过结合组织胺受体而发挥抗组织胺作用,故异丙嗪对紫外线诱导的角质形成细胞对IL-6的分泌可能有某种作用。本研究探讨异丙嗪对中波紫外线(UVB)辐射诱导HaCaT细胞产生IL-6的抑制作用。     

紫外线引起皮肤色素沉着的机制

紫外线引起的皮肤色素沉着包括速发色素沉着和迟发色素沉着。紫外线可通过黑素细胞内的一些分子作用引起皮肤色素沉着 ,但其它细胞也参与色素沉着的发生 ,其中角质形成细胞起非常重要的作用。角质形成细胞可通过旁分泌因子影响黑素细胞黑素的生成。     

干细胞在皮肤光老化治疗方面的研究进展

皮肤作为机体天然屏障,不仅影响机体健康,在外貌、美容等方面同样重要,但随着时间的推移以及外界环境因素尤其紫外线辐射影响,会诱发多种皮肤损伤问题,如氧化应激、皮肤老化、炎症反应、色素沉积甚至癌变。干细胞是一类具有自我复制能力及多向分化潜能的细胞,其强大的旁分泌功能,在抗皮肤光损伤中发挥重要保护作用。本文就紫外线引起的皮肤光老化问题综述干细胞对皮肤的光保护作用及机制,可为临床皮肤病的治疗提供更多可靠依据。     

茶多酚对紫外线辐射后的角质形成细胞和成纤维细胞增生影响的保护作用

紫外线辐射(UVR)是皮肤生物性损伤的主要因素,而皮肤角质形成细胞和成纤维细胞是此生物损伤过程中受到影响的主要细胞[1]。本实验通过MTT法(四甲基偶氮唑盐)研究不同剂量的中波紫外线(UVB)和长波紫外线(UVA),对体外培养的人角质形成细胞株HaCaT和皮肤成纤维细胞增生的影响,并探讨具有抗氧化作用的茶多酚(teapolyphenol,TPP)对此影响的保护作用。1材料和方法1.1主要仪器和试剂酶联检测仪(Clinibio公司),紫外线辐照仪(Sigma公司,UVB光谱峰值为310～315nm,UVA为365nm),96孔培养板(Costar公司),DMEM培养基(Gibeco公司),小牛血清(杭…     

The UV response of the skin: a review of the MAPK, NFκB and TNFα signal transduction pathways

The sun emits different types of ultraviolet (UV) light. Our skin is a natural target of UV radiation which is involved in vitamin D₃ production in our body. UV radiation at high doses is an environmental carcinogen which can elicit skin damage as well as inducing skin cancer. It can mediate inflammatory and immunological reactions through activation of receptors, DNA/RNA damage and production of reactive oxygen species. It is also involved in the release of pro-inflammatory cytokines, of which TNFα has been implicated in tumorigenic activities. In order to mediate its effects, UV radiation is known to activate multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and NFκB pathways in skin cells. The role each of these pathways plays in mediating the release of cytokines such as TNFα remains to be fully characterized. Once the function of these pathways is known, this information may provide for the formulation of therapy which will prevent the release of immunosuppressive cytokines resulting in a reduction in skin cancer formation.     

紫外线辐射前后HaCaT及人成纤维细胞分子伴侣蛋白质组的差异分析

目的初步探讨紫外线辐射所致皮肤细胞分子伴侣蛋白质组整体变化规律。方法分别提取30mJ/cm2UVB照射前后角质形成细胞HaCaT株和10J/cm2UVA照射前后成纤维细胞的总蛋白,采用固相pH梯度双向凝胶电泳技术进行分离,经Imaging Master 2D软件分析以发现差异表达蛋白,并对部分差异表达蛋白进行基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱分析,测定其肽质量指纹图谱,在网上蛋白质数据库检索鉴定差异蛋白。采用Western免疫印迹法对部分质谱鉴定的差异蛋白做进一步验证。结果获得良好的双向电泳图谱,图像分析显示在紫外线辐射前后很多蛋白质发生差异表达,对差异表达的部分蛋白点进行肽质量指纹图谱分析,经Mascot软件检索人非冗余蛋白质数据库后,在UVB辐射后角质形成细胞中鉴定出3个表达显著增加的分子伴侣蛋白:热休克蛋白70KDa 9B、热休克蛋白60KDa和PHB;在UVA辐射后成纤维细胞中鉴定出4个表达显著增加的分子伴侣蛋白:热休克蛋白70KDa A5、热休克蛋白70KDa9B、蛋白二硫键异构酶和PHB。Western免疫印迹法进一步验证上述结果。对这些蛋白的功能和与紫外线辐射的可能关系进行了初步探讨。结论紫外线辐射可以诱导皮肤细胞分子伴侣蛋白质组发生改变,而这些蛋白的变化可能与皮肤细胞应对紫外线辐射并清除其损伤相关。     

Possible involvement of enhanced prostaglandin E2 production in the photosensitivity in xeroderma pigmentosum group A model mice

Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Therefore, XPA-deficient mice are a useful model of human XP and represent a promising tool for photobiologic studies of the disorder. Exposure to ultraviolet (UV) B (280-320 nm) radiation greatly enhanced inflammation and immunosuppression in these mice. To investigate the molecular mechanisms of enhanced UV inflammation and immunosuppression, we determined the amount of prostaglandin (PG) E2, an inflammatory mediator and immunomodulator, and analysed the expression of cyclooxygenase (COX) mRNA in the ear skin of XPA-deficient mice after UV irradiation. In XPA-deficient mice, the amount of PGE2 significantly increased at 48 and 72 h after UVB irradiation to the level that was 8- and 16-fold higher than those in wild-type mice, respectively. The expression level of COX-2 mRNA increased in a time-dependent manner, although COX-1 mRNA was constantly expressed. Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrogated local immunosuppression, and decreased the amount of PGE2 in the ear skin of XPA-deficient mice. These results indicate that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation may induce COX-2 expression. The induced production of PGE2 may be involved in the enhanced inflammation and immunosuppression caused by UV radiation in XPA-deficient mice and XP patients.     

皮肤光老化和抗氧化剂研究进展

皮肤光老化是指皮肤长期受紫外线(ultraviolet,UV)辐射引起的皮肤老化。紫外线可通过诱导活性氧和脂质过氧化物丙二醛生成,诱导金属蛋白酶类表达等途径诱发皮肤光老化。针对光老化的发病机制采用各种天然或合成抗氧化剂能够有效的预防和缓解皮肤光损伤,本文对皮肤光老化机制及治疗研究进展进行综述。     

Towards standardization of UV eye protection: what can be learned from photodermatology?

While knowledge about standardization of skin protection against ultraviolet radiation (UVR) has progressed over the past few decades, there is no uniform and generally accepted standardized measurement for UV eye protection. The literature provides solid evidence that UV can induce considerable damage to structures of the eye. As well as damaging the eyelids and periorbital skin, chronic UV exposure may also affect the conjunctiva and lens. Clinically, this damage can manifest as skin cancer and premature skin ageing as well as the development of pterygia and premature cortical cataracts. Modern eye protection, used daily, offers the opportunity to prevent these adverse sequelae of lifelong UV exposure. A standardized, reliable and comprehensive label for consumers and professionals is currently lacking. In this review we (i) summarize the existing literature about UV radiation‐induced damage to the eye and surrounding skin; (ii) review the recent technological advances in UV protection by means of lenses; (iii) review the definition of the Eye‐Sun Protection Factor (E‐SPF®), which describes the intrinsic UV protection properties of lenses and lens coating materials based on their capacity to absorb or reflect UV radiation; and (iv) propose a strategy for establishing the biological relevance of the E‐SPF.     

The role of cytokines in UV-induced systemic immune suppression

Exposure to ultraviolet radiation induces skin cancer. In addition, UV exposure suppresses the immune response. The mechanism by which skin exposure to UV induces systemic immune suppression is not entirely clear, but a role for cytokines secreted by irradiated epidermal cells has been described. Ultimately, these immune regulatory cytokines affect antigen presenting cell function at distant sites. We describe here preliminary findings suggesting that one consequence of UV exposure is an alteration of IL-12 production by lymph node dendritic cells that result in impaired immune function.     

Effects of whole-body UVB irradiation on cytokine production by peripheral blood mononuclear cells from stage I melanoma patients

Abstract  Ultraviolet (UV) radiation causes significant impairment of immunological function in human skin. The immunosuppressive effects of UV radiation are thought to be due to local release of cytokines by human keratinocytes, leading to impaired function of epidermal antigen-presenting cells (APC) and failure to induce cutaneous delayed-type hypersensitivity (DTH) reactions. Recent studies have shown that individuals susceptible to UV-induced suppression of DTH may be more prone to develop skin cancer including malignant melanoma (MM). Since the causal relationship between UV radiation and the induction of MM still seems obscure, we investigated the immunological reactions of peripheral blood mononuclear cells (PBMC) to whole-body irradiation with UVB in 15 stage I melanoma patients as compared to PBMC from normal volunteers matched for age, gender and skin type. Whole-body irradiation was performed with 0.8 minimal erythema dosages on five consecutive days. Peripheral blood was obtained before and after the procedure. Overall, there were no major effects of UVB irradiation on peripheral lymphocyte subsets and proliferation of PBMC from patients or normal controls, but UVB irradiation led to a significant increase in PWM-stimulated production of IL-6, IL-2R and TNF by PBMC. These changes were independent of the individual UVB dosages administered and appeared in both groups similarly. UVB irradiation did not lead to significant changes on IL-1 and IL-2 expression by PBMC. Our results suggest that PBMC participate in the cytokine response to UV, even in the absence of inflammatory reactions, but that this participation is not specific to MM patients. Received: 4 November 1999 / Revised: 15 March 2000 / Accepted: 17 March 2000     

Klinik und Pathogenese UV‐induzierter Pigmentveränderungen

Solar and ultraviolet (UV) radiation, respectively, are the strongest stimuli for the induction of pigmentation in human skin. UV radiation induces pigmentation by exerting direct and indirect effects on melanocytes. Melanogenesis is a very complex process whose molecular mechanisms are not yet completely understood. Acute UV exposure induces the non‐protective immediate pigment darkening as well as delayed tanning which exerts photoprotective effects. Chronic UV exposure causes permanent pigmentary changes by inducing solar lentigines and pigmented actinic keratoses as well hypopigmentated areas. Artificial UV irradiation (UVA, PUVA) can also induce pigmentary disorders, including lentigines. Since the therapeutic options for UV‐induced pigmentary changes are limited consequent protection as a prophylactic measure is recommended.     

UV radiation induces CXCL5 expression in human skin

CXCL5 has recently been identified as a mediator of UVB‐induced pain in rodents. To compare and to extend previous knowledge of cutaneous CXCL5 regulation, we performed a comprehensive study on the effects of UV radiation on CXCL5 regulation in human skin. Our results show a dose‐dependent increase in CXCL5 protein in human skin after UV radiation. CXCL5 can be released by different cell types in the skin. We presumed that, in addition to immune cells, non‐immune skin cells also contribute to UV‐induced increase in CXCL5 protein. Analysis of monocultured dermal fibroblasts and keratinocytes revealed that only fibroblasts but not keratinocytes displayed up regulated CXCL5 levels after UV stimulation. Whereas UV treatment of human skin equivalents, induced epidermal CXCL5 mRNA and protein expression. Up regulation of epidermal CXCL5 was independent of keratinocyte differentiation and keratinocyte‐keratinocyte interactions in epidermal layers. Our findings provide first evidence on the release of CXCL5 in UV‐radiated human skin and the essential role of fibroblast‐keratinocyte interaction in the regulation of epidermal CXCL5.     

Nrf2/ARE在抗光老化中的作用及机制研究进展

光老化是皮肤长期暴露于紫外线,引起的慢性损伤。既往研究表明氧化应激是造成皮肤急慢性炎症的主要原因,甚至引起细胞突变,以致肿瘤的形成,而紫外线的照射是引起氧化应激主要原因之一。当紫外线照射下产生过多的活性氧(reactive oxygen species,ROS),超过机体清除能力,可影响相关信号通路传导,导致光老化和癌变。最近的研究提示NF-E2相关因子2(NF-E2 related factor2,Nrf2)是参与细胞氧化应激反应的关键因子,通过结合下游的抗氧化反应元件(antioxidant response element,ARE)在细胞防御保护中发挥重要作用,能有效抵御紫外线照射引起的皮肤损伤。该文就Nrf2/ARE在抗光老化中的作用及相关机制的研究作一综述。