Melatonin inhibits senescence-associated melanin pigmentation through the p53-TYR pathway in human primary melanocytes and the skin of C57BL/6 J mice after UVB irradiation.

UVB exposure accelerates skin aging and pigmentation. Melatonin effectively regulates tyrosinase (TYR) activity and aging. The purpose of this study was to determine the association between premature senescence and pigmentation, and the mechanism of melanin synthesis effected by melatonin. Primary melanocytes were extracted and identified from the male foreskin. To inhibit TYR expression, primary melanocytes were transduced with the lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR. The wild-type TYR(+/+) and TYR(-/-) or TYR(+/-) knockout C57BL/6 J mice were used to determine the role of TYR on melanin synthesis in vivo. Results showed that UVB-induced melanin synthesis is dependent on TYR in primary melanocytes and mice. Furthermore, in primary melanocytes pretreated with Nutlin-3 or PFT-α to up or downregulate p53, results showed that premature senescence and melanin synthesis increased in primary melanocytes after UVB irradiation at 80 mJ/cm2, and further increased after being treated with Nutlin-3, while significantly decreased with PFT-α. In addition, melatonin inhibited UVB-induced premature senescence associated with inactivation of p53 and phosphorylation of p53 on Ser15 (ser-15), a decrease of melanin synthesis accompanied by reduced TYR expression. Moreover, skin erythema and pigmentation induced by UVB were reduced in the dorsal and ear skin of mice topically pretreated with 2.5% melatonin. These indicate that melatonin inhibits UVB-induced senescence-associated pigmentation via the p53-TYR pathway in primary melanocytes and prevents pigmentation obviously in the dorsal and ear skin of C57BL/6 J mice after UVB irradiation. KEY MESSAGES: P53 links UVB irradiation-induced senescence and senescence-associated pigmentation and regulates TYR in primary melanocytes after UVB irradiation. Melatonin inhibits senescence-associated pigmentation through the p53-TYR pathway in primary melanocytes. Melatonin prevents skin erythema and melanin pigmentation induced by UVB irradiation in the dorsal and ear skin of C57BL/6J mice.

Traveling wave of inflammatory response to regulate the expansion or shrinkage of skin erythema.

Many skin diseases show circular red lesions on the skin, called erythema. Erythema is characterized by the expansion of its circular area solely from local stimulation. A pathological inflammatory response caused by the stimulation persistently increases inflammatory mediators in the dermis, whereas a normal inflammatory response transiently increases mediators, resulting in the shrinkage of the erythema. Although the diffusion of mediators theoretically reproduces the expansion, how the inflammatory response expands or shrinks the erythema remains unknown. A possibility is positive feedback, which affects mediator production and can generate two distinct stable states (i.e., inflamed and noninflamed), referred to as bistability. Bistability causes a state transition either from the noninflamed to inflamed state or the reverse direction by suprathreshold stimulation. Additionally, the diffusion selectively causes state transition in either direction, resulting in spatial spread of the transited state, known as the traveling wave. Therefore, we hypothesize that the traveling wave of the inflammatory response can account for both the expansion and shrinkage. Using a reaction-diffusion model with bistability, we theoretically show a possible mechanism in which the circular inflamed area expands via the traveling wave from the noninflamed to the inflamed state. During the expansion, the boundary between the inflamed and noninflamed areas moves at a constant velocity while maintaining its concentration gradient. Moreover, when the positive feedback is weak, the traveling wave selectively occurs from the inflamed to noninflamed state, shrinking the inflamed area. Whether the inflamed area expands or shrinks is mainly controlled by the balance of mediator concentration between the noninflamed and inflamed states, relative to the threshold. The traveling wave of the inflammatory response provides an experimentally testable framework for erythema expansion and shrinkage, thereby contributing to the development of effective treatments, including probiotics.

Green Tea Catechin Association with Ultraviolet Radiation-Induced Erythema: A Systematic Review and Meta-Analysis.

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose-response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25-1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: -0.35; 95% CI, -0.57 to -0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.

The association of photo-induced collagen degeneration and the development of telangiectasias in rosacea.

Rosacea is a chronic, often progressive disorder characterized by facial erythema, telangiectasias, papules, pustules, and/or rhinophyma. In this study, we investigated the tissue structure in rosacea compared to controls. We performed a case-control study between five patients with mild-to-moderate erythematotelangiectatic rosacea (ETR) and five matched controls. Facial biopsy samples from rosacea patients and controls were stained with picrosirius red for collagen and CD31 for microvessel identification. Mean collagen content was significantly greater in control samples (19.603% ±8.821%) compared to rosacea samples (16.812% ± 7.787%, p = 0.030). In contrast, mean microvessel density was significantly higher in rosacea patients (4.775 E-5 ± 1.493 E-5 µm-3 ) compared to controls (2.559 E-5 ± 8.732 E-6 µm-3 , p = 0.004). Mean microvessel lumen area was also significantly higher in rosacea patients (491.710 ± 610.188 µm2 ) compared to controls (347.879 ± 539.624 µm2 , p = 0.003). We identified a correlation between decreased collagen content and increased microvessel size and density in rosacea patients that was not observed in controls. These structural changes to the dermal matrix may contribute to the characteristic vessel growth and dilation in rosacea.

Comparison of mechanical, chemical and physical human models of in vivo skin damage: Randomized controlled trial.

INTRODUCTION: Human in vivo models of skin damage were often used in research of cutaneous disorders. The most commonly used models were tape-stripping as mechanical, sodium lauryl sulphate-induced irritation as chemical and ultraviolet radiation as physical damage model. In regard to differences between models, they were expected to have different responses to damage and recovery, with unique skin parameters' changes over time. OBJECTIVE: The aim was to compare skin parameters in three different skin damage models on the same anatomical location, with and without topical treatment. METHODS: Four test sites on each forearm were randomly assigned to three skin damage models with the fourth sites on each forearm chosen as a control, undamaged site. Skin parameters were assessed using non-invasive methods. RESULTS: Sodium lauryl sulphate irritation caused the strongest damage with delayed reaction to the irritant. Tape stripping leads to highest initial skin barrier disruption but afterwards it showed the fastest skin recovery. Ultraviolet radiation did not affect skin barrier function, but it elevated skin erythema and melanin level. Tested preparation did not lead to changes in measured parameters. CONCLUSION: The skin of the participants had different response to three skin damage models with distinct changes of skin parameters and recovery. The trial was registered at ClinicalTrials.gov under the identifier NCT03783819.

Epidermal barrier changes in patients with psoriasis: The role of phototherapy.

BACKGROUND: Some skin diseases may modify epidermal barrier function. Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Phototherapy is an option for treating psoriasis, but little is known about how epidermal barrier function is modified by phototherapy in psoriatic patients. OBJECTIVES: (a) To compare skin homeostasis between involved and uninvolved skin in psoriatic patients with healthy controls (b) To evaluate changes in the epidermal barrier function in psoriatic patients treated with phototherapy. METHODS: Sixty patients with plaque-type psoriasis and sixty gender and age-matched healthy controls were enrolled. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity, erythema and melanin index were measured using non-invasive tools in the healthy control and involved and uninvolved psoriatic skin before and after phototherapy. RESULTS: Healthy controls had lower TEWL and erythema index and higher SCH than psoriatic patients, both at uninvolved psoriatic skin and psoriasis plaques. TEWL was higher at psoriasis plaques than at uninvolved skin (19.20 vs 11.57 g/h/m2 ; P < .001). Following phototherapy, a decreasing trend was observed for TEWL, of 1.03 (SD 0.75) and 0.97 (SD 0.81) g/h/m2 for uninvolved and involved skin respectively. SCH was significantly lower at psoriatic plaques than at uninvolved skin (7.32 vs 36.62Arbitrary Units [AU]; P < .001). SCH increased by 1.15AU (SD 0.26) on psoriatic plaques after the phototherapy session (P < .001). CONCLUSION: Psoriatic plaques showed epidermal barrier dysfunction compared to uninvolved skin and healthy controls. Phototherapy may improve epidermal barrier function in psoriatic patients. SCH increased after a phototherapy session on the psoriatic plaques.

[Mechanism of Inhibitory Effects of Cherry Bark-containing Jumihaidokuto on Benzoyl Peroxide Induced Erythema in Hairless Mice].

Benzoyl peroxide (BPO) has been widely used to treat acne vulgaris. Skin flaking, erythema and skin irritation have been observed as side effects of BPO in the treatment of this disorder. In a clinical study, cherry bark-containing jumihaidokuto significantly reduced the erythema induced by BPO application. However, its mechanism of action has not been clarified. In the present study, an application of 10% BPO caused erythema and an increase in interleukin (IL)-1α in the skin of hairless mice, and these changes were significantly suppressed by cherry bark-containing jumihaidokuto at 600 mg/kg. In addition, using a three-dimensional cultured human epidermis model (LabCyte EPI-MODEL), cherry bark-containing jumihaidokuto extract at 250 or 500 µg/mL significantly suppressed IL-1α mRNA expression induced by the application of 0.2 mM BPO. Therefore, cherry bark-containing jumihaidokuto may have suppressed BPO-induced erythema by inhibiting the increase in the IL-1α level in the skin.

Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis.

Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.

Epidermal Langerhans cells resistance to solar-simulated radiation in actinic prurigo patients with low minimal erythema dose.

BACKGROUND: Actinic prurigo is a chronic photodermatosis of unclear pathogenesis. Epidermal Langerhans cell resistance to migration after ultraviolet radiation exposure has been proposed as a possible mechanism, as occurs in polymorphic light eruption patients. The purpose of this study was to evaluate the effect of solar-simulated radiation (SSR) on epidermal Langerhans cells in the uninvolved skin of actinic prurigo patients. PATIENTS AND METHODS: Fifteen patients with actinic prurigo participated in the study. A biopsy from the uninvolved and unirradiated skin of the left buttock was performed, and another from the uninvolved skin of the right buttock, 72 hours after exposure to two MEDs of SSR. Immunohistochemistry staining was used to identify Langerhans cells (CD1a) in all samples. RESULTS: In actinic prurigo patients with normal MED, there was a significant decrease in the number of epidermal Langerhans cells on the buttock skin exposed to two MED of SSR compared with the unirradiated buttock skin (P = .02 and .035 respectively). On the contrary, in patients with low MED there were no significant differences in the number of epidermal Langerhans cells between irradiated and unirradiated skin (P = .39). CONCLUSION: Epidermal Langerhans cells migration after ultraviolet radiation exposure is decreased in actinic prurigo patients with low MED as has been reported in PLE patients, especially, those with low MED or positive UVB provocation tests. Langerhans cells resistance could be part of a common pathogenic mechanism in these two photodermatoses.

Research Techniques Made Simple: Cutaneous Colorimetry: A Reliable Technique for Objective Skin Color Measurement.

Skin color evaluation contributes to assessment of an individual's cutaneous phenotype. Skin color changes provide important clues to disease progression or treatment response. Skin color is also a predictor of skin cancer risk. Melanin pigment, blood flow, skin thickness, and photoaging contribute to skin color. Melanin, hemoglobin, bilirubin, and carotene are the primary chromophores of skin color. Their concentrations vary depending on the individual's phenotype, anatomic location, external insults of chemical irritants and UVR, and physiological changes. The evaluation and perception of skin color are often subjective. Objective quantification of skin color can be achieved with colorimetric devices such as tristimulus colorimeters. These devices compute the intensity of light reflected from skin and correlate with pigmentation and erythema. Cutaneous color and color changes can be quantified under color organization systems, such as the CIELAB color space, which is standardized by the Commission Internationale de l'Eclairage (CIE). The CIELAB expresses color's lightness, red/green intensity, and yellow/blue intensity, as L*, a*, and b* values, respectively. Additionally, skin color's full spectral characteristics and cutaneous physiology can be measured with spectrophotometers. This article outlines basic principles of the CIELAB color system and how to optimally use colorimetric devices as a skin research tool.

Rubeosis faciei diabeticorum is not associated with oxidative stress and skin autofluorescence.

BACKGROUND: Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. OBJECTIVE: Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . METHODS: Patients diagnosed with Type 2 diabetes mellitus (n=32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p≤0.05 was considered statistically significant. RESULTS: There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ=0.398, p=0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. STUDY LIMITATIONS: This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. CONCLUSIONS: The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.

Rubeosis faciei diabeticorum is not associated with oxidative stress and skin autofluorescence

Abstract Background Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. Objective Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . Methods Patients diagnosed with Type 2 diabetes mellitus (n = 32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p ≤ 0.05 was considered statistically significant. Results There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ = 0.398, p = 0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. Study limitations This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. Conclusions The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.

In vivo Change of Keratin-Bound Molecules in the Human Stratum Corneum following Exposure to Ultraviolet Radiation.

BACKGROUND/OBJECTIVES: Ultraviolet (UV) radiation damages the stratum corneum (SC) and disrupts the skin barrier. The damaged skin changes in the molecular composition of the SC, including its water content. However, it is difficult to examine the in vivo SC changes with existing methods, so those have not been well characterized. Therefore, we investigated in vivo changes of UV-induced SC damage using confocal Raman spectroscopy. METHOD: We irradiated the volar forearm of 10 subjects with 0.5, 1, and 1.5 minimal erythemal doses of UV radiation. Then, we examined erythema, the transepidermal water loss (TEWL), the water content, the natural moisturizing factor (NMF), and the lipids of the skin. RESULTS: After UV irradiation, erythema and TEWL of the skin were both increased. The bound water content of the SC was also increased following UV irradiation. The NMF of the SC revealed different tendencies. All free amino acids (FAAs) of the NMF were increased after UV irradiation, except proline. trans-urocanic acid, pyrrolidone carboxylic acid, lactate, and urea, which are NMF components produced by the subsequent catabolism of FAAs and sweat, were decreased after UV irradiation. The amount of ceramide in the SC was also decreased after UV exposure, while cholesterol was increased. CONCLUSIONS: The bound water content of the SC was increased by UV exposure along with increasing TEWL, several NMF components, and cholesterol. These in vivo results for UV-damaged SC obtained via Raman spectroscopy could be applied to research with regard to protecting the SC from UV radiation and treating UV-damaged SC.

The Reparative Effect of Dendrobium officinale Protocorms against Photodamage Caused by UV-Irradiation in Hairless Mice.

Dendrobium officinale protocorms (DOPs) are a specific developmental stage of Dendrobium officinale KIMURA et MIGO, which is used in folk medicine to ease skin issues, such as wrinkles and erythema. The purpose of the current study was to evaluate the effect of DOPs on UV irradiation-induced skin damage in bc_nu hairless mice, using matrixyl as a positive control. Hairless mice were randomly separated into 6 groups (8 mice per group). The normal control group received solvent and was not exposed to UV irradiation, while the model control group received solvent and was exposed to UV irradiation. The positive control group was subjected to UV irradiation and then received a 10 mg/mL formulation of matrixyl. The DOPs-treated groups received a transdermal application of a DOPs formulation after 4 weeks of UV irradiation. Relevant indicators, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS) and matrix metalloproteinases (MMPs), were then used to evaluate the ability of DOPs to repair photodamage. The results indicated that DOPs significantly reduced erythema and protected the skin from dryness and therefore exhibits a significant anti-photoaging effect. In addition, the expression of CAT, SOD, and GSH-Px increased while TBARS and MMPs levels decreased in DOPs-treated mice. This demonstrated that DOPs can inhibit photodamage in the skin of hairless mice. DOPs could be used as a potential therapeutic agent to protect the skin against UV-induced photoaging.

Annona muricata extract containing pharmaceutical emulgels with and without penetration enhancer for depigmenting and antierythmic effects.

The basic purpose of this research work was to investigate the skin depigmenting and antierythmetic effects of emulgel containing Annona muricata L. fruit extract by comparing it with its control and the variation in these effects with the addition of penetration enhancer. The control (without extract and penetration enhancer i.e. clove oil 8%) and the two test formulations with 4% fruit extract FA and FB (without clove oil and with clove oil) were formulated and evaluated for in vitro characteristics (pH, conductivity and in vitro release). The emulgels were then applied on the cheeks of 26 healthy female human volunteers (n=26) for a study period of 12 weeks. Skin melanin and erythema contents were measured by Mexameter at base line and then after every 2 weeks. Both the test formulations showed significant decrease in melanin and erythema contents when compared to control but FB showed marked decrease in skin melanin when compared to the FA. While in case of skin erythema, the effects of FA were greater as compared to other formulation. When paired sample t test (5% level of significance) was applied, the test formulations showed significant results. This study reveals that the Annona muricata L. fruit extract naturally contains some important phenolic compounds and can be effectively used in topical preparations for the treatment of skin hyperpigmentation and dermatitis. Skin whitening effects can be increased by the addition of penetration enhancer.

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice.

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.

Keratosis pilaris rubra with mucin deposition.

Keratosis pilaris (KP) is a benign cutaneous disorder characterized by folliculocentric hyperkeratotic papules most often occurring on the proximal extremities. Erythema is usually limited to perifollicular skin, but when keratosis pilaris presents on a background of confluent erythema, the term keratosis pilaris rubra (KPR) is used. The histological findings associated with KP have not been well described in the literature. Herein, we present a case of a 14-year-old male with a 7-year history of erythema and follicular-based papules over his bilateral cheeks, consistent with KPR. Histological examination revealed abundant mucin, keratotic follicular plugging, and periadnexal lymphocytosis. Our novel finding of abundant dermal mucin expands the histopathologic description of KPR.

Clinical and Biological Characterization of Skin Pigmentation Diversity and Its Consequences on UV Impact.

Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, and the various methodologies for skin color assessment. Then, melanocyte activity and amount, type and distribution of melanins, which are the main drivers for skin pigmentation, are described. Paracrine regulators of melanocyte microenvironment are also discussed. Skin response to sun exposure is also highly dependent on color diversity. Thus, sensitivity to solar wavelengths is examined in terms of acute effects such as sunburn/erythema or induced-pigmentation but also long-term consequences such as skin cancers, photoageing and pigmentary disorders. More pronounced sun-sensitivity in lighter or darker skin types depending on the detrimental effects and involved wavelengths is reviewed.

Acetyl-11-keto-ß-boswellic acid inhibits the secretion of cytokines by dendritic cells via the TLR7/8 pathway in an imiquimod-induced psoriasis mouse model and in vitro.

AIMS: Psoriasis vulgaris is mediated by T and dendritic cells. This study aimed to investigate the effects of acetyl-11-keto-ß-boswellic acid (AKBA) on activated dendritic cells (DCs) using an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated with resiquimod (R848) in vitro. MATERIALS AND METHODS: The mice were treated with IMQ and intragastrically administered 25-100 mg/kg/day of AKBA, 1 mg/kg/day of methotrexate (MTX), or normal saline. The inflammation of skin lesions in IMQ mice were evaluated by psoriasis area and severity index (PASI) and pathological staining. The related proteins of Toll-like receptor (TLR)7/8 pathways were assessed using Western blotting, and the expression levels of interleukin (IL)-23 and IL-12p40 mRNA using reverse transcription-polymerase chain reaction. The numbers of DCs and marker-positive BMDCs were assessed using flow cytometry and the levels of inflammatory factors using the enzyme-linked immunosorbent assay. KEY FINDINGS: AKBA and MTX obviously improved the psoriasis-like skin lesions of IMQ-treated mice. AKBA also obviously decreased the PASI score, reduced the thickness of epidermis, ameliorated the infiltration of CD3+ and CD11c+ cells in skin lesions, decreased the activation of local DCs, inhibited the mRNA expression and secretion of inflammatory factors IL-12 and IL-23, inhibited the maturation and differentiation of DCs to promote T-cell differentiation, and inhibited the activation of TLR7/8 and IRF signaling pathways. SIGNIFICANCE: This study implied that AKBA might have an anti-inflammatory effect on psoriasis by inhibiting the maturation and activation of DCs via the TLR8 and IRF signaling pathways.