Constitutive Pigmentation Research Articles

The effect of visible light and near-infrared radiation on constitutive pigment of patients with vitiligo

British Journal of DermatologyVolume 163, Issue 1 p. 211-213 Correspondence The effect of visible light and near-infrared radiation on constitutive pigment of patients with vitiligo I. Seo, I. Seo Models and Methods Department, Johnson and Johnson Consumer Companies, Skillman, NJ 08558-9418, U.S.A.Search for more papers by this authorA. Baqer, A. Baqer Department of Dermatology, Al-Sabah Hospital, Ministry of Public Health, KuwaitSearch for more papers by this authorN. Kollias, N. Kollias Models and Methods Department, Johnson and Johnson Consumer Companies, Skillman, NJ 08558-9418, U.S.A.Search for more papers by this author I. Seo, I. Seo Models and Methods Department, Johnson and Johnson Consumer Companies, Skillman, NJ 08558-9418, U.S.A.Search for more papers by this authorA. Baqer, A. Baqer Department of Dermatology, Al-Sabah Hospital, Ministry of Public Health, KuwaitSearch for more papers by this authorN. Kollias, N. Kollias Models and Methods Department, Johnson and Johnson Consumer Companies, Skillman, NJ 08558-9418, U.S.A.Search for more papers by this author First published: 24 June 2010 https://doi.org/10.1111/j.1365-2133.2010.09761.xCitations: 3 Nikiforos Kollias. E-mail: NKollia@its.jnj.com Conflicts of interest: none declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume163, Issue1July 2010Pages 211-213 RelatedInformation

La couleur de la peau humaine : de la recherche à l’esthétique

Skin color is controlled by pigmentary genes that regulate constitutive skin pigmentation and by environmental factors, the most obvious of them being solar U.V. At this time, more than 130 distinct pigmentary genes are known. They affect embryogenesis and survival of the melanocyte system, mélanosome biogenesis, melanogenesis, mélanosome transport and transfer, eumelanins/pheomelanins ratio and epidermal mélanosome turn-over and elimination. The pigmentary disorders of the skin are common and represent an important part of dermatologist activity. They concern at the same time the general dermatology and the aesthetic dermatology.

Short- and Long-Term Effects of UV Radiation on the Pigmentation of Human Skin

The incidence of skin cancer, including cutaneous melanoma, has risen substantially in recent years, and epidemiological and laboratory studies show that UV radiation is a major causative factor of this increase. UV damage also underlies photoaging of the skin, and these deleterious effects of UV can be, in part, prevented in skin with higher levels of constitutive pigmentation. We review the clinical studies we have made in recent years regarding the rapid and the long-term responses of the pigmentary system in human skin to UV exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 32-35; doi:10.1038/jidsymp.2009.10.

Upwards and onwards

The success of a journal is ultimately tied to its appeal to its readership and potential authors. Over the past few years, by publishing News and Views on high profile papers in the field, inserting ‘Melanoma’ into the title and being adopted as the official journal of the Society for Melanoma Research, and generally acting as a focus and forum for debate on key issues, Pigment Cell & Melanoma Research has increased its readership and is now attracting papers from groups that until recently would have submitted elsewhere. The increased awareness of the journal means that papers published in pcr are more widely read and research into pigment cell biology is gaining a higher profile. The most visible manifestation of a journal’s success is the impact factor, used by publishers to trumpet the success of a journal, and by authors as a key determinant of where to submit. With that in mind, it is again satisfying that the impact factor of this journal has risen yet again, to 4.634. The strong upward trend in impact factor reflects increased citation of papers published in pcr and suggests that the journal is achieving its ambition of serving the research community by publishing papers and reviews of increasing significance to the field. The fact that many of the most cited papers and reviews are in the melanoma field also suggests that the decision to court a melanoma audience has benefited the journal as a whole and is making a substantial contribution to its success. One of the most obvious manifestations of genetic diversity is the range of human pigmentation phenotypes as illustrated by this month’s striking cover. It is widely believed that early hominids originated as a hair covered species in Africa, lacking epidermal pigmentation except in exposed sites and that pigmentation evolved to protect skin against photodamage as hair cover diminished. The migration of humans out of Africa subsequently led to a gradual decrease in levels of constitutive pigmentation as a result of the evolutionary pressures arising from the need to synthesise vitamin D. However, the fact that pigmented melanocytes are present in a wide range of sites that are not sun exposed suggests that melanin-loaded pigment cells may have a range of functions not directly related to UV-irradiation. The hypothesis from Elias et al. explores the possibility that stress to the epidermis also contributed substantially to the origins of human pigmentation. Since its isolation in 1994, the gene encoding the microphthalmia-associated transcription factor Mitf has assumed centre stage as a key factor controlling melanocyte development and differentiation. Over recent years, it has also been implicated as a major regulator of cell cycle progression and metastatic potential. Given its importance and its regulation by the MAPkinase and Wnt/β-catenin signaling pathways implicated in both developmental control of the melanocyte lineage and melanoma progression, it seemed inevitable that genetic lesions affecting the MITF gene would be found in melanoma. That prophecy was fulfilled with the observation that amplification of the MITF gene occurs in many melanoma patients, though interestingly even a 100-fold amplification only led to around 1.5-fold increase in MITF protein levels. Nevertheless, the amplification of the MITF gene spurred the quest to find more subtle genetic alterations that would affect MITF activity and consequently melanoma behavior. Now, in this issue, Cronin et al. report that MITF is mutated at several residues in melanoma that lead to altered MITF function. The paper, featured in a News and Views by David Fisher, also highlights mutations in Sox10, a key regulator of MITF expression. Together, the evidence suggests that de-regulation of MITF function or expression is a major determinant of melanoma progression and lends support to the idea that understanding more of the controls operating on MITF may open novel therapeutic avenues.

Long‐lasting pigmentation of human skin, a new look at an overlooked response to UV

Long‐lasting pigmentation of human skin, a new look at an overlooked response to UV

Dermal contributions to UVA‐induced oxidative stress in skin

When the skin is exposed to solar irradiation, UVA photons interact with skin tissues and induce excessive reactive oxygen species, resulting in oxidative stress. We have shown in a previous study that in vivo chemiluminescence's measurement can be used to evaluate the overall level of UVA-induced oxidative stress in human skin. However, the origin of the observed chemiluminescence signals remains unclear. UVA-induced chemiluminescence measurements were conducted: (a) in vitro on collagen solutions and solid collagen sheet preparations, (b) ex vivo on human and mouse skin biopsies, and (c) in vivo on human skin of various constitutive pigmentation levels. Fluorescence was measured on collagen in vitro as well as on skin for the in vivo experiments. We found in the in vitro experiments that UVA-induced chemiluminescence increases with the presence of collagen cross-links. When dermal sides were exposed to UVA irradiation, both mouse and human skin biopsies demonstrated significantly higher chemiluminescence levels than when epidermal sides were exposed to UVA. The amount of collagen cross-links decreases slightly following UVA exposure, as shown both by in vivo fluorescence and by UVA-induced chemiluminescence. Finally, there was less measurable UVA-induced chemiluminescence in dark skin compared with light pigmented skin in vivo. The dermis is very sensitive to UVA photons. Dermal cross-links are potential UVA sensitizers. The oxidative stress induced by UVA and measured by chemiluminescence may largely be attributed to the breakdown of dermal collagen cross-links.

Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV irradiation

Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation.

Tanning, p53 and PCMR

Tanning, p53 and PCMR

In vivomeasurement of skin erythema and pigmentation: new means of implementation of diffuse reflectance spectroscopy with a commercial instrument

Various physical, chemical and biological insults, including exposure to ultraviolet (UV) radiation, cause erythema and change in pigmentation in human skin. These reactions provide an important measure of the cutaneous response to the insult. To present a new implementation of a method for objective in vivo measurement of erythema and pigmentation. The method is based on acquisition of reflectance spectra in the visible range using a commercially available spectrophotometer. The probe of this instrument incorporates an integrating sphere that captures the light remitted from the skin in a wide range of angles. We corrected the acquired reflectance spectra for the contribution of specular reflections by an amount given by the Fresnel equation and verified this correction experimentally. This correction is particularly important when measurements are performed on heavily pigmented skin. The corrected reflectance spectra are then transformed into absorbance spectra. To analyse these spectra, we developed an algorithm which can be used to calculate apparent concentrations of oxyhaemoglobin, deoxyhaemoglobin and melanin. This method was tested in clinical studies of skin reactions induced by exposure to UV radiation. These experiments involved three groups of subjects with progressively darker complexion (constitutive pigmentation). Each group consisted of 10 subjects. Erythema was measured 1 day after UV exposure, and pigmentation (melanin content) 1 week later. Results Distinct apparent absorbance spectra were obtained for dark, intermediate and fair skin. There was good agreement between reconstructed spectra and experimental data at relevant wavelengths. Difference absorption spectra were able to show the dose dependence of UV-induced responses, and erythema and pigmentation values obtained by the spectroscopic method showed good correlation with those derived by subjective visual grading. The results demonstrate that the presented methodology provides an objective noninvasive way of measuring UV-induced reactions independently of the level of constitutive pigmentation.

Skin Differences, Needs, and Disorders across Global Populations

Accurately determining the incidence and prevalence of dermatologic disease in most large populations has been challenging for reasons ranging from the lack of easily quantifiable tests and measures to imprecision around definitions of race, ethnicity, photo skin type, pigmentation, and population groups. Compounding the problems with these categorizations is the fact that skin disease and skin health are affected not just by inherent risk factors but also by habits and environment. Thus, a fundamental question remains as we evaluate the effects of cultural and environmental factors: do genetic factors account for most of the difference that we see in skin types? Is the primary influence the way the skin mediates the environmental insult of UV radiation or how inflammation is handled? Is melanization the primary characteristic that we should measure and consider? This article will provide an introduction to current knowledge and future directions researchers are taking in differentiating both the biological differences of skin and the clinical manifestations of skin disease among the groups described above. This discussion will be followed by a brief overview of cultural practices and environmental factors that are known to have significant impact on skin disease and a summary of the most common conditions that are encountered worldwide.

β‐Defensin 3: a novel and unexpected key that unlocks the melanocortin 1 receptor

β‐Defensin 3: a novel and unexpected key that unlocks the melanocortin 1 receptor

Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Breast Cancer Risk in a Multiethnic Population

Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35-79 years from the San Francisco Bay Area of California (1995-2003). In-person interviews were obtained for 1,788 newly diagnosed cases and 2,129 controls. Skin pigmentation measurements were taken on the upper underarm (a sun-protected site that measures constitutive pigmentation) and on the forehead (a sun-exposed site) using reflectometry. Biospecimens were collected for a subset of the study population (814 cases, 910 controls). A high sun exposure index based on reflectometry was associated with reduced risk of advanced breast cancer among women with light constitutive skin pigmentation (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91). The association did not vary with VDR genotype. No associations were found for women with medium or dark pigmentation. Localized breast cancer was not associated with sun exposure or VDR genotype. This study supports the hypothesis that sunlight exposure reduces risk of advanced breast cancer among women with light skin pigmentation.

Pigmentation after single and multiple UV-exposures depending on UV-spectrum

Minimal pigmentation dose (MMD) after a single UV-exposure is well investigated. Whereas only few studies have established MMD after multiple UV-exposures and mainly in fair-skinned persons. The purpose of this study was to establish MMD 1 week after, respectively, one and five UV-exposures in volunteers with a large variation in constitutive pigmentation. A total of 52 volunteers (skin Types II-V) had skin pigmentation quantified by reflectance spectroscopy. They were UV-exposed on the back for 1 and 5 days using a Solar Simulator, narrowband UVB, broadband UVA and UVA1. For all sources a higher dose was needed the more pigmented the skin, except for UVA1. After one UV-exposure, we found a significant positive linear correlation between UV-dose to one MMD, skin type and pre-exposure skin pigmentation. After five UV-exposures the positive linear correlation between UV-dose and MMD and skin type was only significant for narrow band UVB, pre-exposure skin pigmentation was significant also for Solar Simulator. For UVA and particularly UVA1 the MMD was independent of pre-exposure pigmentation. The number of SED to MMD is therefore almost the same for very fair-skinned and dark-skinned persons. Pre-exposure pigmentation was clearly more predictive of MMD than skin type. 50% of MMD equals a pigmentation increase of 1%. The shorter the wavelengths the higher the SED to produce MMD. Solar was the least melanogenic and UVA1 the most melanogenic. For the UVB-sources a higher dose was needed the more pigmented the skin. For UVA the MMD was independent of pre-exposure pigmentation.

Human skin pigmentation: melanocytes modulate skin color in response to stress

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary (e.g., during pregnancy) or permanent (e.g., during aging) changes in skin color, environmental factors (e.g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically (as therapy for pigmentary diseases) and cosmeceutically (e.g., to design tanning products with potential to reduce skin cancer risk).

Human pigmentation variation: Evolution, genetic basis, and implications for public health

Pigmentation, which is primarily determined by the amount, the type, and the distribution of melanin, shows a remarkable diversity in human populations, and in this sense, it is an atypical trait. Numerous genetic studies have indicated that the average proportion of genetic variation due to differences among major continental groups is just 10-15% of the total genetic variation. In contrast, skin pigmentation shows large differences among continental populations. The reasons for this discrepancy can be traced back primarily to the strong influence of natural selection, which has shaped the distribution of pigmentation according to a latitudinal gradient. Research during the last 5 years has substantially increased our understanding of the genes involved in normal pigmentation variation in human populations. At least six genes have been identified using genotype/phenotype association studies and/or direct functional assays, and there is evidence indicating that several additional genes may be playing a role in skin, hair, and iris pigmentation. The information that is emerging from recent studies points to a complex picture where positive selection has been acting at different genomic locations, and for some genes only in certain population groups. There are several reasons why elucidating the genetics and evolutionary history of pigmentation is important. 1) Pigmentation is a trait that should be used as an example of how misleading simplistic interpretations of human variation can be. It is erroneous to extrapolate the patterns of variation observed in superficial traits such as pigmentation to the rest of the genome. It is similarly misleading to suggest, based on the "average" genomic picture, that variation among human populations is irrelevant. The study of the genes underlying human pigmentation diversity brings to the forefront the mosaic nature of human genetic variation: our genome is composed of a myriad of segments with different patterns of variation and evolutionary histories. 2) Pigmentation can be very useful to understand the genetic architecture of complex traits. The pigmentation of unexposed areas of the skin (constitutive pigmentation) is relatively unaffected by environmental influences during an individual's lifetime when compared with other complex traits such as diabetes or blood pressure, and this provides a unique opportunity to study gene-gene interactions without the effect of environmental confounders. 3) Pigmentation is of relevance from a public health perspective, because of its critical role in photoprotection and vitamin D synthesis. Fair-skinned individuals are at higher risk of several types of skin cancer, particularly in regions with high UVR incidence, and dark-skinned individuals living in high latitude regions are at higher risk for diseases caused by deficient or insufficient vitamin D levels.

Population-Based Study of Natural Variation in the Melanocortin-1 Receptor Gene and Melanoma

Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene is associated with constitutive pigmentation phenotypes and development of melanoma and nonmelanoma skin cancers. We investigated the effect of MC1R variants on melanoma using a large, international population-based study design with complete determination of all MC1R coding region variants. Direct sequencing was completed for 2,202 subjects with a single primary melanoma (controls) and 1,099 subjects with second or higher-order primary melanomas (cases) from Australia, the United States, Canada, and Italy. We observed 85 different MC1R variants, 10 of which occurred at a frequency >1%. Compared with controls, cases were more likely to carry two previously identified red hair ("R") variants [D84E, R151C, R160W, and D294H; odds ratio (OR), 1.6; 95% confidence interval (95% CI), 1.1-2.2]. This effect was similar among individuals carrying one R variant and one r variant (defined as any non-R MC1R variant; OR, 1.6; 95% CI, 1.3-2.2) and among those carrying only one R variant (OR, 1.5; 95% CI, 1.1-1.9). There was no statistically significant association among those carrying only one or two r variants. Effects were similar across geographic regions and categories of pigmentation characteristics or number of moles. Our results confirm that MC1R is a low-penetrance susceptibility locus for melanoma, show that pigmentation characteristics may not modify the relationship of MC1R variants and melanoma risk, and suggest that associations may be smaller than previously reported in part due to the study design.

Relationship between skin response to ultraviolet exposure and skin color type

Sun exposure is responsible for detrimental damage ranging from sunburn to photoaging and skin cancer. This damage is likely to be influenced by constitutive pigmentation. The relationship between ultraviolet (UV) sensitivity and skin color type was analyzed on 42 ex vivo skin samples objectively classified from light to dark skin, based on their values of individual typology angle (ITA) determined by colorimetric parameters. The biologically efficient dose (BED) was determined for each sample by quantifying sunburn cells after exposure to increasing doses of UV solar-simulated radiation. Typical UV-induced biologic markers, other than erythema, such as DNA damage, apoptosis and p53 accumulation, were analyzed. A statistically significant correlation was found between ITA and BED and, ITA and DNA damage. Interestingly, DNA lesions were distributed throughout the whole epidermal layers and the uppermost dermal cells in light, intermediate and tanned skin while they were restricted to suprabasal epidermal layers in brown or dark skin. Our data support, at the cellular level, the relationship between UV sensitivity and skin color type. They emphasize the impact of DNA damage accumulation in basal layer in relation to the prevalence of skin cancer.

Melanin content and MC1R function independently affect UVR‐induced DNA damage in cultured human melanocytes

Malignant transformation of melanocytes leads to melanoma, the most fatal form of skin cancer. Ultraviolet radiation (UVR)-induced DNA photoproducts play an important role in melanomagenesis. Cutaneous melanin content represents a major photoprotective mechanism against UVR-induced DNA damage, and generally correlates inversely with the risk of skin cancer, including melanoma. Melanoma risk is also determined by susceptibility genes, one of which is the melanocortin 1 receptor (MC1R) gene. Certain MC1R alleles are strongly associated with melanoma. We hereby present experimental evidence for the role of two melanoma risk factors, constitutive pigmentation, as assessed by total melanin, eumelanin and pheomelanin contents, and MC1R genotype and function, in determining the induction and repair of DNA photoproducts in cultured human melanocytes after irradiation with increasing doses of UVR. We found that total melanin and eumelanin contents (MC and EC) correlated inversely with the extent of UVR-induced growth arrest, apoptosis and induction of cyclobutane pyrimidine dimers (CPD), but not with hydrogen peroxide release in melanocytes expressing functional MC1R. In comparison, melanocytes with loss-of-function MC1R, regardless of their MC or EC, sustained more UVR-induced apoptosis and CPD, and exhibited reduced CPD repair. Therefore, MC, mainly EC, and MC1R function are independent determinants of UVR-induced DNA damage in melanocytes.

The photoadaptive response to ultraviolet exposure in human skin using ultraviolet spectrophotometry

Both pigmentation and non-pigmentary processes contribute to the development of photoadaptation yet the exact contribution of either in the resting state and in response to ultraviolet (UV) radiation is unclear. The purpose of this study was to estimate independently these changes occurring in the epidermis following repeated exposure to UV in two groups with differing degrees of constitutive pigmentation. We describe a mathematical model for explaining the spectral absorbance of excised human epidermis based on the absorbance of constituent chromophores. The model was applied to spectral absorbance data measured on samples of epidermis excised from pre-irradiated skin and from skin obtained following UV irradiation on 3 successive days. We found that in Asian skin there was only a mild photoadaptive response, principally by a small increase in pigmentation. On the other hand, the significant adaptive response in Caucasian skin was through hyperplasia of the epidermis, with tanning contributing only to a much smaller degree. This study has enabled us to study independently the pigmentary and non-pigmentary pathways and has shown that in those people with a lower degree of constitutive pigment, the primary mechanism of photoadaptation is via the non-pigmentary route.

α-Melanocortin and Endothelin-1 Activate Antiapoptotic Pathways and Reduce DNA Damage in Human Melanocytes

UV radiation is an important etiologic factor for skin cancer, including melanoma. Constitutive pigmentation and the ability to tan are considered the main photoprotective mechanism against sun-induced carcinogenesis. Pigmentation in the skin is conferred by epidermal melanocytes that synthesize and transfer melanin to keratinocytes. Therefore, insuring the survival and genomic stability of epidermal melanocytes is critical for inhibiting photocarcinogenesis, particularly melanoma, the most deadly form of skin cancer. The paracrine factors alpha-melanocortin and endothelin-1 are critical for the melanogenic response of cultured human melanocytes to UV radiation. We report that alpha-melanocortin and endothelin-1 rescued human melanocytes from UV radiation-induced apoptosis and reduced DNA photoproducts and oxidative stress. The survival effects of alpha-melanocortin and endothelin-1 were mediated by activation of the melanocortin 1 and endothelin receptors, respectively. Treatment of melanocytes with alpha-melanocortin and/or endothelin-1 before exposure to UV radiation activated the inositol triphosphate kinase-Akt pathway and increased the phosphorylation and expression of the microphthalmia-related transcription factor. Treatment with alpha-melanocortin and/or endothelin-1 enhanced the repair of cyclobutane pyrimidine dimers and reduced the levels of hydrogen peroxide induced by UV radiation. These effects are expected to reduce genomic instability and mutagenesis.