UVA的致癌作用不容忽视

以往的观点认为,短波紫外线(UVB)可致癌,而长波紫外线(UVA)虽可使皮肤老化,却并不损伤DNA ,但目前澳大利亚悉尼大学Agar等的一项研究显示,UVA对皮肤基底层所造成的损伤比UVB更为严重。(ProcNatAcadSciUSA 2 0 0 4年3月2 3日在线发表)研究人员应用激光捕获显微切割(LCM)技术对2种不同类型的皮肤恶性病变进行了研究。结果显示,在日光性角化病(一种癌前病变)样本中,所有UVB所致突变都位于表皮上层结构,而UVA所致突变5 7%位于基底层;在鳞状细胞癌(SCC)样本中,UVB所致损伤82 %位于表皮上层结构,而UVA所致突变86 %位于基底层。由…     

低温治疗通过p38 MAPK信号通路抑制UVB诱导的小鼠皮肤炎症北大核心CSCD

目的探讨局部低温治疗对中波紫外线辐射(UVB)诱导的皮肤炎症的作用机制。方法角质形成细胞体外培养后接受如下3种处理:仅低温治疗、仅UVB照射、UVB照射后低温治疗,检测低温治疗对UVB照射后角质形成细胞的作用。将野生型雌性C57BL/6小鼠分为3组:低温治疗组、UVB组、UVB+低温治疗组。通过数字测微计测量、组织病理学、免疫组织化学、免疫荧光、定量RT-PCR和Western blot检测低温治疗对UVB诱导炎症的影响。结果低温治疗可显著减少UVB诱导的巨噬细胞和T细胞浸润(P<0.05),并显著抑制UVB诱导的p38磷酸化(P<0.05),减少相关的炎症反应,包括减轻耳肿胀反应、表皮增生(P<0.05)和皮肤炎症(P<0.05),减少小鼠模型中相关细胞因子表达和细胞凋亡(P<0.05)。结论低温治疗是治疗UVB诱导的皮肤炎症的一种有效的方法。     

早期皮肤T细胞淋巴瘤的紫外线B光疗法

皮肤T细胞淋巴瘤(CTCL)是一种原发于皮肤,以后逐渐累及淋巴结以及内脏,进展缓或的疾病,其皮肤的改变开始为红色斑别,进一步发展成硬结状的斑块,最后可演变为溃疡甚至发生癌变.因为CTCL最常发生在身体非暴露部位,有人认为紫外线B(UVB)照射可能起到保护作用.目前对早期CTCL治疗应用最广的方法是局部外用盐酸氮芥,电子束照射和口服补骨脂素加UVA光疗法,涉及UVB光疗法的     

p38丝裂原活化蛋白激酶信号转导通路在紫外线诱导表皮细胞凋亡中的作用

大量流行病学调查及分子生物学实验研究表明：紫外线可通过诱导活性氧及细胞因子产生DNA损伤和基因表达的改变导致细胞凋亡,这个过程非常复杂,有多个信号转导途径参与.由于细胞凋亡与皮肤癌的发生密切相关,近年来UVB诱导表皮细胞凋亡引起了人们广泛的关注.p38丝裂原活化蛋白激酶（p38MAPK）是细胞内重要的信号传导系统之一,参与细胞生长、发育、分化和凋亡等一系列生理、病理过程.p38MAPK可被紫外线激活,并在紫外线诱发的细胞应答过程中发挥重要的作用.     

金属硫蛋白对皮肤癌发生抵抗作用及机制的研究

目的:建立Ha Ca T细胞UVB损伤模型,给予硫酸锌刺激,探讨其对细胞损伤的拮抗作用及机制。方法:细胞分为正常组、加锌组、紫外线组、加锌紫外线组,照射前24 h给予硫酸锌处理,UVB照射后继续培养,确定硫酸锌给药浓度和UVB辐射时间,Western blot法检测细胞凋亡情况,免疫细胞化学方法检测金属硫蛋白和NF-κB/p65的表达情况。结果:紫外线组细胞内Bax/Bcl-2比值高于正常组和加锌紫外线组;紫外线组、加锌组细胞内MT表达水平均高于正常组,加锌紫外线组细胞MT表达水平高于紫外线组;紫外线组细胞内NF-κB/p65表达水平高于正常组和加锌紫外线组细胞。结论:硫酸锌能够通过细胞内金属硫蛋白的表达,缓解UVB诱发Ha Ca T细胞凋亡的发生。     

紫外线对人皮肤成纤维细胞老化损伤的影响

目的:研究紫外线对人皮肤成纤维细胞的老化损伤及c-fos、c-jun、Sirt1蛋白在UVA诱导损伤后的变化。方法:原代培养人皮肤成纤维细胞,采用MTT法测定第5代细胞经不同强度、不同作用时间UVA照射后人成纤细胞的增殖情况,采用SA-β-Gal染色法观察细胞衰老情况,酶联免疫吸附试验(ELISA)测定细胞内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶活性(GSH-Px)及金属基质蛋白酶-1(MMP-1)含量,免疫组化法观察细胞内c-fos、c-jun的表达,实时定量PCR法检测cfos、c-jun、Sirt1 mRNA的表达,Western blot检测c-fos、c-jun、Sirt1蛋白表达。结果:经5 J/cm~2、10 J/cm~2、20 J/cm~2UVA照射72 h后,人皮肤成纤维细胞的增殖能力减弱,人皮肤成纤维细胞在UVA照射下普遍被诱导成衰老状态,经SA-β-Gal染色后观察到细胞衰老明显,不同强度UVA照射能明显降低细胞内SOD、GSH-Px活性,显著提高MMP-1的含量。免疫组化结果显示c-fos、c-jun表达呈阳性,同时c-fos、c-jun、Sirt1的mRNA和蛋白表达水平均显著升高。结论:UVA能诱导人皮肤成纤维细胞形态改变,这一过程与紫外线强度及作用时间相关,经照射后c-fos、c-jun、Sirt1的表达明显升高,启动了光老化的进程。     

中波紫外线对皮肤免疫细胞的作用研究

紫外线诱导皮肤免疫抑制一直是光学免疫领域的研究热点,而中波紫外线(UVB)是引起皮肤免疫抑制作用的主要光谱,其对皮肤免疫细胞的作用是紫外线诱导皮肤免疫抑制的关键,皮肤中主要的免疫细胞大致也可分为固有免疫细胞和非固有免疫细胞,固有免疫细胞包括皮肤朗格汉斯细胞(LC)、肥大细胞、单核巨噬细胞、角质形成细胞(KC)、NK细胞;非固有免疫细胞主要包括T淋巴细胞、B淋巴细胞.研究UVB对皮肤固有免疫细胞和非固有免疫细胞的影响很有意义.     

紫外线诱导人皮肤成纤维细胞形态改变及对基质金属蛋白酶表达的影响

目的研究紫外线(UVB)诱导人皮肤成纤维细胞中端粒长度及基质金属蛋白酶(MMPs)的变化,及其在UVB诱导光老化中的作用。方法原代培养人成纤维细胞,用第5代细胞进行UVB照射处理。观察细胞形态,实时定量PCR检测COL1a1和h TERT的mRNA表达细胞端粒长度,Western blot检测MMP-3和MMP-1蛋白。结果 30 m J/cm2UVB照射人成纤维细胞24 h后,细胞逐渐变圆、皱缩和排列紊乱;COL1a1和TERT的mRNA水平表达显著升高,基质金属蛋白酶MMP-3和MMP-1蛋白水平也显著升高,端粒长度显著缩短。结论 UVB可能诱导人皮肤成纤维细胞形态改变,及MMP-3和MMP-1的表达明显升高,启动了光老化的早期进程。     

没食子儿茶素没食子酸酯对中波紫外线辐射后树突状细胞功能的影响

目的 观察没食子儿茶素没食子酸酯（epigallocatechin gallate，EGCG）对中波紫外线（UVB）辐射后树突状细胞（DC）功能的影响并探讨其可能的机制。方法 分离外周血单核细胞，经细胞因子诱导DC成熟后，再使用不同剂量的UVB照射DC，将经EGCG处理或未处理的DC与淋巴细胞进行混合培养，72h后用MTF法检测DC刺激淋巴细胞增殖能力；用流式细胞术分析DC表面CDS0、CD86、HLA-DR、CD40分子表达的变化；酶联免疫吸附试验（ELISA）检测DC培养24h后上清液中IL-10及IL-12分泌水平。结果UVB以剂量依赖的方式抑制DC刺激同种异体淋巴细胞增殖能力，并以剂量依赖的方式抑制DC表面共刺激分子的表达；使用浓度为200μg／ml的EGCG处理DC后，各剂量组UVB所致的免疫抑制作用均可得到部分改善，与单纯照光组相比，UVB＋EGCG组的抑制率分别比同剂量UVB组减少了60．0％、60．4％、59．2％、40．8％及12．2％，当EGCG浓度大于100μg／ml时，EGCG对DC表面共刺激分子的表达有促进作用；UVB照射对DCIL-12及IL-10因子的分泌未有显著影响，经EGCG处理并照射UVB的DCIL-12分泌水平显著降低，但IL-10分泌水平显著提高（P〈0．05）。结论 EGCG具有调节中波紫外线辐射后DC细胞免疫功能的作用，其作用与促进DC表面共刺激分子表达及影响其IL-12及IL-10分泌有关。     

亚硒酸钠对UVB损伤人角质形成细胞的保护作用

目的:研究亚硒酸钠(Na2Se O3)对中波紫外线(UVB)损伤人角质形成细胞的保护作用。方法:培养永生化人角质形成细胞(Ha Ca T细胞),实验分为4组处理:(1)正常对照组;(2)Na2Se O3组:分别加入1 nmol/L、10 nmol/L、50 nmol/L、100 nmol/L、200 nmol/L和1μmol/L的Na2Se O3预孵育24 h;(3)UVB组:300、600和900 J/m2UVB照射;(4)Na2Se O3+UVB组:Na2Se O3预孵育24 h后进行UVB照射。采用MTT法检测细胞增殖活性,采用流式细胞仪检测300 J/m2UVB照射后细胞的凋亡率。结果:(1)UVB组与正常对照组比较,细胞增殖活性显著降低(P0.05),细胞活性与UVB照射剂量呈负相关;(2)Na2Se O3组与正常对照组比较,细胞增殖活性无明显差异;(3)不同浓度Na2Se O3+UVB组与UVB组比较,细胞增殖活性增加,差异显著(P0.05),其中100 nmol/L组促进细胞增殖作用最强;(4)300 J/m2UVB照射后,不同浓度Na2Se O3+UVB组与UVB组比较,凋亡率下降,差异显著(P0.05),其中100 nmol/L组抑制凋亡作用最强。结论:UVB对角质形成细胞有损伤作用,且与照射剂量呈正相关;Na2Se O3具有光保护性能,可减轻UVB辐射损伤人角质形成细胞。     

Solar ultraviolet-induced DNA damage response: Melanocytes story in transformation to environmental melanomagenesis

Exposure to sunlight is both beneficial, as it heats the planet to a comfortable temperature, and potentially harmful, since sunlight contains ultraviolet radiation (UVR), which is deemed detrimental for living organisms. Earth's ozone layer plays a vital role in blocking most of the extremely dangerous UVC; however, low frequency/energy UVR (i.e., UVB and UVA) seeps through in minute amount and reaches the Earth's surface. Both UVB and UVA are physiologically responsible for a plethora of skin ailments, including skin cancers. The UVR is readily absorbed by the genomic DNA of skin cells, causing DNA bond distortion and UV-induced DNA damage. As a defense mechanism, the DNA damage response (DDR) signaling in skin cells activates nucleotide excision repair (NER), which is responsible for the removal of UVR-induced DNA photolesions and helps maintain the genomic integrity of the cells. Failure of proper NER function leads to mutagenesis and development of skin cancers. One of the deadliest form of skin cancers is melanoma which originates upon the genetic transformation of melanocytes, melanin producing skin cells. NER is a well-studied DNA repair system in the whole skin, as a tissue, but not much is known about it in melanocytes. Therefore, this review encapsulates NER in melanocytes, with a specific focus on its functional regulators and their cross talks due to skin heterogeneity and divulging the potential knowledge gap in the field.     

Pigmented human skin equivalent—as a model of the mechanisms of control of cell-cell and cell-matrix interactions

The melanin pigment system in human skin is extraordinarly well developed and assures the photoprotection of the skin against harmful solar radiation. Specific cell-cell interactions between one melanocytes and keratinocytes play a fundamental role in the regulation of melanogenesis and melanin pigementation, the two key elements of this system, giving rise to the concept of a structural, functional collaborative ‘epidermal melanin unit,’ Early experiments strongly suggested that melanocyte growth and differentiation are regulated by paracrine factors from keratinocytes and other skin cells. In addition, co-culture studies with keratinocytes has shown that the extracellular matrix acts as a local environmental signal for dendrite formation and melanogenesis. Attempts to reconstruct pigmented human skin in vitro have made great progress over the last decade. The behavior of cells in these pigmented human skin equivalents closely resembles that in vivo, and the cells can still respond to appropriate extrinsic regulatory stimuli such as ultraviolet radiation. Keratinocytes and fibroblasts have been shown to be active partners in the regulation of melanocyte distribution, viability and other differentiation functions, presumably by direct contact and the effects of various soluble paracrine factors. By reproducing cell-cell and cell-matrix interactions, these culture systems provide a promising experimental model for investigating regulation of the skin pigmentary system and the role of photoprotection against harmful solar radiation.     

Chaotic solar cycles modulate the incidence and severity of mental illness

This paper hypothesizes that the intensity of ultraviolet radiation (UVR) from the Sun predisposes humans to polygenic mutation fostering major mental illness (MMI) and other disorders of neurodevelopment. In addition, the variation in the intensity of this radiation acts to stress immune systems, possibly mediated by cytokines, resulting in variable clinical expressions of mental illness and autoimmune disorders. Organisms can adapt to chronic high-intensity UVR by producing melanin and by retaining various pigments. We found that 28% of 11-year solar cycles produce particularly severe solar flares during which UVR is 300% more intense and hence more damaging than normal. Out of a total of six severe cycles in the past 250 years, four have occurred in the past 55 years, possibly explaining the apparent increase in the incidence of MMI in recent decades. UVR is 10 times more mutagenic than ionizing radiation to nuclear DNA, and especially damaging to mitochondrial DNA. However, variable light as manifested by seasons stresses adaptability to UVR, possibly through an immune mechanism. We show that the region of the Earth having the most UVR, relative to the most variation in that light, is at 54 +/-10 degrees (N or S) latitude. Therefore, the most potential damage from sunlight occurs between the Equator and the Poles, not at the Equator itself. The human brain, our most important organ of adaptability, must be able to survive environmental variation, with successful matching to the environment resulting in adaptation. Unsuccessful adaptation to UVR (and possibly other types of radiation) results in mutation, which can produce neuro-chemical abnormalities manifested by MMI. We postulate that the combination of intensity and variation in UVR serves as a global modulator of MMI.     

Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress

The skin is a known target organ for the proopiomelanocortin (POMC)-derived neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin, and ACTH and also a source of these peptides. Skin expression levels of the POMC gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but are determined by such factors as the physiological changes associated with hair cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune cytokine release, or the presence of cutaneous pathology. Among the cytokines, the proinflammatory interleukin-1 produces important upregulation of cutaneous levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates expression of all the components of the CRH/POMC system including expression of the corresponding receptors. Molecular characterization of the cutaneous POMC gene shows mRNA forms similar to those found in the pituitary, which are expressed together with shorter variants. The receptors for POMC peptides expressed in the skin are functional and include MC1, MC5 and mu-opiate, although most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors for CRH are also present in the skin. Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses. The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a function analogous to the HPA axis, that in the skin is expressed as a highly localized response which neutralizes noxious stimuli and attendant immune reactions.     

Passive cutaneous anaphylaxis in the rat, induced with two homologous reagin-like antibodies, and its specific inhibition with disodium cromoglycate

Rats immunized with egg albumin and Bordetella pertussis organisms produce a `mast cell sensitizing' antibody (MCSAb) which is thermolabile, a potent skin sensitizer and reagin in character. Similarly the immune response to Nippostrongylus brasiliensis in rats is closely associated with the formation of antibodies which also resembles human reagins. Homologous passive cutaneous anaphylactic (PCA) reactions induced by N. brasiliensis serum were found to be similar to those produced using the adjuvant induced antibody in that both were completely inhibited by, combined treatment with mepyramine and 2-bromo-D-lysergic acid diethylamide (BOL148), cyproheptadine or pretreatment with compound 48/80. In contrast, skin reactions involving passive sensitization of rats with rabbit hyperimmune antiserum were much less affected. Studies on mast cell disruption at the site of PCA reactions showed that such reactions using N. brasiliensis serum were accompanied by degranulation of mast cells, and confirmed that mast cell damage occurs in PCA induced with MCSAb. Both the PCA and the mast cell disruption were maximal 5 minutes after antigen challenge in both rat reagin systems. The skin reaction produced using rabbit hyperimmune antiserum was not primarily dependent on, or associated with, mast cell disruption, since it was still possible to induce skin reactions when the mast cells had been disrupted by compound 48/80, and skin reactions could be obtained without significant mast cell disruption.

Disodium cromoglycate, a new compound introduced for the treatment of asthma, was shown to inhibit both the PCA and mast cell disruption induced using both rat reagin antibodies but not the skin reactions produced with rabbit anti-serum. It was possible to obtain substantial inhibition of mast cell disruption induced by rat reagin, even when the PCA was inhibited only slightly. At higher doses the discharge of the mediators from mast cells was also prevented. This interference with mast cell permeability was not unspecific since disodium cromoglycate did not prevent the skin reaction or mast cell disruption produced by compound 48/80. As expected mepyramine was able to partially inhibit the skin reaction without affecting mast cell disruption induced by rat reagin or compound 48/80. It is suggested that disodium cromoglycate acts at some critical pathway in the events after the union of antigen with reagin antibody and that this critical pathway might be common to both the human and rat reagin systems.

     

Blood stasis contributions to the perception of skin pigmentation

The chromatic characteristics of skin color arise from the interactions of light (primarily absorption and scattering) with the epidermis and the dermis. The primary light absorbers in skin are hemoglobin and melanin. Most of scattering is attributed to collagen fibers and in pigmented skin to melanosomes. Traditionally skin redness is considered to arise due to locally elevated concentrations of hemoglobin, whereas skin pigmentation is attributed to melanin. In this study we attempt to understand better the contributions of these chromophores to the perceived skin color using spectral analysis of skin color reactions induced by ultraviolet (UV) irradiation or pressure. In the first experiment 12 individuals with skin phototypes III-IV were irradiated on the back using a solar simulator with doses ranging from 0.7 to 3 MED. The skin reactions were evaluated on days 1, 7, 14, and 21 after irradiation. Evaluations included diffuse reflectance spectroscopy (DRS) and clinical assessment of the erythema and the pigment reaction. Apparent concentrations of melanin, oxy-, and deoxy-hemoglobin were calculated from the absorption spectra. In the second experiment the levels of deoxy-hemoglobin of the volar forearm of ten volunteers were selectively altered by either application of a pressure cuff or by topical application of 3% H(2)O(2). Changes in skin color appearance were documented by photography, colorimetry, and DRS. In the UV exposure experiment all reactions were dose dependent. Oxy-hemoglobin values increased to a maximum on day 1, correlating well with the clinical evaluation of erythema, and then decreased exponentially to base line. Melanin showed a significant increase on day 7 and remained relatively constant for the next 3 weeks, correlating well with the clinical evaluation of pigmentation (tanning). Deoxy-hemoglobin increased slightly on day 1 and remained elevated for the next 2 weeks. Thus, deoxy-hemoglobin correlated moderately with the clinical erythema scoring on day 1 only, while it contributes significantly to what is clinically perceived as skin tanning on days 7 and 14. Application of pressure below the diastolic level increased deoxy-hemoglobin concentration as measured by DRS. This increase corresponded to a decrease of a "pigmentation" parameter (based on the L(*)a(*)b(*) scale) in a similar fashion that has been documented for increases in melanin concentration. Topical H(2)O(2) application reduced deoxy-hemoglobin levels as measured by DRS. This reduction coincided kinetically with a visible skin blanching. Application of pressure or H(2)O(2) did not significantly alter the levels of oxy-hemoglobin or melanin. In this report we present compelling evidence that deoxy-hemoglobin significantly contributes to the skin color appearance. Blood pooling, expressed as increased deoxy-hemoglobin, can contribute to what is visually perceived as pigmentation. Furthermore, we present that measurement of its contribution to the skin color appearance can only be accomplished with DRS.     

A new method for photodynamic therapy of melanotic melanoma -- effects of depigmentation with violet light photodynamic therapy

Melanotic melanomas have a poor response to photodynamic therapy (PDT). The reason for this is that melanin absorbs light over the entire wavelength region used for PDT (400-750 nm). Photobleaching of melanin is an approach to overcome this obstacle. In the present work, reflectance spectroscopy was applied to study depigmentation of human and murine skin with different melanin contents, and effects induced by PDT with topical application of methyl 5-aminolevulinate (MAL) on B16F10 melanotic melanomas transplanted to nude mice. Depigmentation and inhibition of tumor growth after violet light (420 nm) exposure, red light (634 nm) exposure, and combinations of both were studied. Reflectance spectroscopy was suitable for evaluation of the pigmentation of both human and murine skin. Skin depigmentation leads to increase in reflectance. PDT with violet light bleached some of the melanin in the skin above the B16F10 melanomas, and possibly also in the upper part of the melanomas. This resulted in a larger growth inhibition of tumors first given PDT with violet light and then with red light compared to treatments using the reverse order of illumination, namely, red light before violet light. It is concluded that violet light PDT can bleach melanin in melanotic tumors and therefore increase their sensitivity to red light PDT. This finding indicates a new PDT modality that can be further developed for treatment of superficial melanotic melanomas and possibly other diseases where pigmentation is a problem.     

Mitigating thermal mechanical damage potential during two-photon dermal imaging

Two-photon excitation fluorescence microscopy allows in vivo high-resolution imaging of human skin structure and biochemistry with a penetration depth over 100 microm. The major damage mechanism during two-photon skin imaging is associated with the formation of cavitation at the epidermal-dermal junction, which results in thermal mechanical damage of the tissue. In this report, we verify that this damage mechanism is of thermal origin and is associated with one-photon absorption of infrared excitation light by melanin granules present in the epidermal-dermal junction. The thermal mechanical damage threshold for selected Caucasian skin specimens from a skin bank as a function of laser pulse energy and repetition rate has been determined. The experimentally established thermal mechanical damage threshold is consistent with a simple heat diffusion model for skin under femtosecond pulse laser illumination. Minimizing thermal mechanical damage is vital for the potential use of two-photon imaging in noninvasive optical biopsy of human skin in vivo. We describe a technique to mitigate specimen thermal mechanical damage based on the use of a laser pulse picker that reduces the laser repetition rate by selecting a fraction of pulses from a laser pulse train. Since the laser pulse picker decreases laser average power while maintaining laser pulse peak power, thermal mechanical damage can be minimized while two-photon fluorescence excitation efficiency is maximized.     

Raman spectroscopy of in vivo cutaneous melanin

We successfully acquire the in vivo Raman spectrum of melanin from human skin using a rapid near-infrared (NIR) Raman spectrometer. The Raman signals of in vivo cutaneous melanin are similar to those observed from natural and synthetic eumelanins. The melanin Raman spectrum is dominated by two intense and broad peaks at about 1580 and 1380 cm(-1), which can be interpreted as originating from the in-plane stretching of the aromatic rings and the linear stretching of the C-C bonds within the rings, along with some contributions from the C-H vibrations in the methyl and methylene groups. Variations in the peak frequencies and bandwidths of these two Raman signals due to differing biological environments have been observed in melanin from different sources. The ability to acquire these unique in vivo melanin signals suggests that Raman spectroscopy may be a useful clinical method for noninvasive in situ analysis and diagnosis of the skin.     

Studies of delayed systemic effects of ultraviolet B radiation (UVR) on the induction of contact hypersensitivity, 2. Evidence that interleukin-10 from UVR-treated epidermis is the critical mediator

Acute, low-dose ultraviolet B radiation (UVR) alters cutaneous immunity at the local site as well as systemically. Within 2-3 days of UVR exposure, recipient mice lose their capacity to develop contact hypersensitivity (CH) when hapten is painted on unexposed skin. This loss correlates temporally with a functional deficit among dendritic antigen-presenting cells within non-draining lymph nodes and spleen. In the experiments described, the delayed systemic immune deficiency following acute, low-dose UVR exposure was found to be eliminated with neutralizing anti-interleukin-10 (IL-10) antibody. Intracutaneous injection of IL-10 generated a deficiency of systemic immunity as well as a functional deficit among lymph node dendritic cells that was similar to that induced by UVR. The skin itself was found to be the source of the IL-10 responsible for these defects, and epidermis (presumably keratinocytes) rather than mast cells was found to be the source of IL-10 within UVR-exposed skin. The potential relationships are discussed between the delayed systemic immune deficit created by acute, low-dose UVR, and the systemic immune deficits caused by chronic, high-dose UVR and by a single, high-dose UVR exposure.