Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain.

Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes.

Natural moisturising factor constituents in South African nursing students.

BACKGROUND: The majority of South African healthcare workers are Black Africans with dark-pigmented skin. Studies on how the markers of skin barrier function and natural moisturising factor (NMF) compare between dark and light-pigmented skin are limited. Quantifying NMF in a nursing student population during their practical training at university may provide valuable insight into their potential susceptibility to skin conditions associated with low NMF. OBJECTIVES: The objectives of this study were to quantify and compare NMF content of Black African, Mixed Race and White nursing students from their dominant dorsal hand. METHODS: Forty-nine White, 32 Black African and 5 Mixed Race nursing students participated in this study. Tape strip samples were collected from the participants' dominant dorsal hand and NMF content was measured, including histidine (HIS), pyrrolidone carboxylic acid (PCA), trans-urocanic acid (t-UCA) and cis-urocanic acid (c-UCA), as well as cytokines interleukin-1 alpha (IL-1α) and interleukin-1 receptor antagonist (IL-1RA). RESULTS: No statistically significant differences in PCA, t-UCA, c-UCA, IL-1α or IL-1RA were found between Black African and White nursing students. HIS was significantly (p = 0.001) higher in White nursing students when compared to Black African students. The ratio of tot-UCA/HIS was significantly higher in Black Africans (p = 0.0002) when compared to White nursing students. CONCLUSION: No significant differences were established in NMF content between White and Black African nursing students, other than HIS which was significantly higher in White students than in Black African students. Different HIS levels between the racial groups suggest variation in histidase activity which may be related to skin pH and pigmentation. This finding may suggest that nursing students at the beginning of their careers may have similar susceptibility to skin diseases related to NMF.

In Vitro Anti-Inflammatory and Antioxidant Activities of pH-Responsive Resveratrol-Urocanic Acid Nano-Assemblies.

Inflammatory environments provide vital biochemical stimuli (i.e., oxidative stress, pH, and enzymes) for triggered drug delivery in a controlled manner. Inflammation alters the local pH within the affected tissues. As a result, pH-sensitive nanomaterials can be used to effectively target drugs to the site of inflammation. Herein, we designed pH-sensitive nanoparticles in which resveratrol (an anti-inflammatory and antioxidant compound (RES)) and urocanic acid (UA) were complexed with a pH-sensitive moiety using an emulsion method. These RES-UA NPs were characterized by transmission electron microscopy, dynamic light scattering, zeta potential, and FT-IR spectroscopy. The anti-inflammatory and antioxidant activities of the RES-UA NPs were assessed in RAW 264.7 macrophages. The NPs were circular in shape and ranged in size from 106 to 180 nm. The RES-UA NPs suppressed the mRNA expression of the pro-inflammatory molecules inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Incubation of LPS-stimulated macrophages with RES-UA NPs reduced the generation of reactive oxygen species (ROS) in a concentration-dependent manner. These results suggest that pH-responsive RES-UA NPs can be used to decrease ROS generation and inflammation.

Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

Stratum corneum biomarkers after in vivo repeated exposure to sub-erythemal dosages of ultraviolet radiation in unprotected and sunscreen (SPF 50+) protected skin.

BACKGROUND: There is a need for non-invasive biomarkers to assess in vivo efficacy of protective measures aiming at reducing ultraviolet radiation (UVR) exposure. Stratum corneum (SC) biomarkers showed to be promising markers for internal UVR dose and immune response. PURPOSE: To establish a dose-response relationship for SC biomarkers and explore their suitability for in vivo assessment of the blocking effect of two sunscreens with a high sun protection factor (SPF) (50+). METHODS: Twelve volunteers were exposed to a broad-spectrum UVB (280-320 nm), five times a week, during one week. Unprotected back skin was irradiated with 0.24, 0.48, 0.72 and 1.44 standard erythema dose (SED) and sunscreen-protected skin with 3.6 SED. SC samples for determination of the relative amount of cis-urocanic acid (cUCA) and thirteen immunological makers including cytokines and matrix metalloproteinases (MMP) were collected after each irradiation. RESULTS: cUCA sharply increased after the first irradiation in a dose-dependent fashion. However, it levelled-off after subsequent exposures and reached a plateau for the highest UV-dose after the third irradiation. None of the immunological markers showed dose-dependency. However, MMP-9, IL-1ß and CCL27 increased gradually from baseline during repetitive exposures to the highest UV-dose. Assessed from cUCA, both sunscreens blocked >98% of the applied UV-dose. CONCLUSIONS: cUCA is a sensitive, non-invasive marker of the internal UVR dose enabling in vivo assessment of the blocking effect of high SPF sunscreens in the UVB-region. Immunological SC markers show low sensitivity in detecting immune response at sub-erythemal UVR dosages, suggesting they might be suitable only at higher and/or repetitive UVR exposure.

Urocanic acid enhances memory consolidation and reconsolidation in novel object recognition task.

Urocanic acid (UCA) is an endogenous small molecule that is elevated in skin, blood and brain after sunlight exposure, mainly playing roles in the periphery systems. Few studies have investigated the role of UCA in the central nervous system. In particular, its role in memory consolidation and reconsolidation is still unclear. In the present study, we investigated the effect of intraperitoneal injection of UCA on memory consolidation and reconsolidation in a novel object recognition memory (ORM) task. In the consolidation version of the ORM task, the protocol involved three phases: habituation, sampling and test. UCA injection immediately after the sampling period enhanced ORM memory performance; UCA injection 6 h after sampling did not affect ORM memory performance. In the reconsolidation version of the ORM task, the protocol involved three phases: sampling, reactivation and test. UCA injection immediately after reactivation enhanced ORM memory performance; UCA injection 6 h after reactivation did not affect ORM memory performance; UCA injection 24 h after sampling without reactivation did not affect ORM memory performance. This UCA-enhanced memory performance was not due to its effects on nonspecific responses such as locomotor activity and exploratory behavior. The results suggest that UCA injection enhances consolidation and reconsolidation of an ORM task, which further extends previous research on UCA effects on learning and memory.

Analytical tools for urocanic acid determination in human samples: A review.

Urocanic acid is a chromophore found in the skin that has been identified as an important immunosuppressant and carcinogenesis mediator through its photoisomerization from trans to cis form induced by ultraviolet radiation. Research on analytical methods that explore urocanic acid isomerization is indispensable to fully understand the deleterious effects mediated by this biomarker. In this context, the current relevant analytical methods for determination of these isomers in human samples are summarized in this review. The methods presented here are applicable to human samples collected by noninvasive methods (or minimally invasive), encompassing an array of analytical techniques, including high-performance capillary electrophoresis, confocal Raman spectroscopy, gas chromatography, high-performance liquid chromatography, and mass spectrometry, among others. Developed high-performance liquid chromatography methods have proven to be advantageous, allowing noninvasive collections for in vivo analysis and the confocal Raman, specially, for real-time analysis. Among all these methods, high-performance liquid chromatography is the most investigated one with mass spectrometry or ultraviolet detector, and the mass spectrometry detector being the most studied in the last years, demonstrating high sensitivity, very low detection limits, and accurate identification, especially for clinical investigations.

Loss-of-function mutations in filaggrin gene and malignant melanoma: a case-control study.

BACKGROUND: Loss-of-function mutations in filaggrin gene (FLG) have been suggested to increase the susceptibility of skin malignancies due to reduced levels of epidermal filaggrin and its degradation products, urocanic acid, which may be protective against ultraviolet irradiation. OBJECTIVE: We aimed to investigate the association between FLG mutation status and the occurrence of malignant melanoma (MM) in Danish adults. METHODS: The prevalence of FLG mutations in a sample of MM biopsies was compared with a FLG-genotyped cohort from two general population studies. Pearson's chi-squared and Fisher's exact tests were used to compare the two groups. RESULTS: A total of 867 MM biopsies and 9965 general population controls were genotyped, respectively. In the MM sample, two (0.23%) individuals were homozygous and 80 (9.4%) were heterozygous mutation carriers. In the general population controls, the prevalence of FLG mutations was 18 (0.18%) and 835 (8.4%) for homozygous and heterozygous mutations, respectively. Fisher's exact test and Pearson's chi-squared test yielded non-significant P-values when the groups were compared. CONCLUSION: FLG mutation was not associated with MM in the studied populations. This finding indicates that epidermal deficiency of filaggrin and its degradation products does not influence the risk of MM significantly.

Topical cis-urocanic acid prevents ocular surface irritation in both IgE -independent and -mediated rat model.

PURPOSE: Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis. METHODS: The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used. In the OA model, an Evans Blue stain concentration of conjunctival tissue was used to evaluate vascular leakage due to allergic reaction. RESULTS: The cis-UCA was well tolerated and effective in both the IgE-independent and -mediated rat models. Treatment with C48/80 caused conjunctival hyperaemia, which was significantly inhibited by ketotifen at the 6 h time point (p = 0.014) and by dexamethasone and cis-UCA 0.5% at 12 (p = 0.004) and 24 (p = 0.004) hour time points. In a comparison between the active drug treatments, only ketotifen showed a significant difference (p = 0.023) to cis-UCA treatment at the 1 h time point, otherwise there were no statistically significant differences between the active drugs. Ketotifen, dexamethasone and cis-UCA 0.5% significantly inhibited the C48/80-induced nuclear accumulation of Ki-67, without differences between the active treatment groups. In the OA model, cis-UCA 0.5% did not inhibit the vascular leakage of conjunctiva, whereas cis-UCA 2.5% of was at least equally effective compared to olopatadine, abolishing the allergic vascular leakage response almost completely. CONCLUSIONS: The present findings in the two AC models suggest that cis-UCA might have anti-allergic potency both in immediate and delayed-type allergic reactions in the eye.

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells.

BACKGROUND: Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%. OBJECTIVE: This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells. METHODS: Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11). RESULTS: Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions. CONCLUSIONS: We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.

Intravesical treatment with cis-urocanic acid improves bladder function in rat model of acute bladder inflammation.

AIMS: The aim was to study the effect of intravesically instilled cis-urocanic acid (cis-UCA) on bladder function in an experimental rat model of acute bladder inflammation. Hyaluronic acid (HA) was used as a comparator compound. METHODS: Bladder irritation was induced in female rats by intravesical hydrochloric acid (HCl) infusion. Vehicle, 0.5% HA, or 2% cis-UCA solutions were infused intravesically twice a day for three consequent days. On the fourth day, urodynamical measurements were performed, the animals were sacrificed, and the bladders were removed for histopathological assessment. RESULTS: HCl treatment caused significant impairment of bladder function indicated by decreased micturition intervals and voided urine volumes and induced severe voiding dysfunction observed as occurrence of overflow incontinence. These functional changes were accompanied by increased bladder weight, hemorrhage, and infiltration of inflammatory cells into the urothelium. Intravesical cis-UCA treatment recovered bladder function by significantly prolonging the micturition interval, increasing the voided volume, and reducing the occurrence of overflow incontinence. All these changes were comparable to the effects of HA. CONCLUSIONS: Intravesical administration of cis-UCA was able to partially recover bladder function impaired by chemical irritation. Cis-UCA may offer a novel intravesical treatment option in some inflammatory conditions of the bladder. Neurourol. Urodynam. 35:786-791, 2016. © 2015 Wiley Periodicals, Inc.

Basis for the gain and subsequent dilution of epidermal pigmentation during human evolution: The barrier and metabolic conservation hypotheses revisited.

The evolution of human skin pigmentation must address both the initial evolution of intense epidermal pigmentation in hominins, and its subsequent dilution in modern humans. While many authorities believe that epidermal pigmentation evolved to protect against either ultraviolet B (UV-B) irradiation-induced mutagenesis or folic acid photolysis, we hypothesize that pigmentation augmented the epidermal barriers by shifting the UV-B dose-response curve from toxic to beneficial. Whereas erythemogenic UV-B doses produce apoptosis and cell death, suberythemogenic doses benefit permeability and antimicrobial function. Heavily melanized melanocytes acidify the outer epidermis and emit paracrine signals that augment barrier competence. Modern humans, residing in the cooler, wetter climes of south-central Europe and Asia, initially retained substantial pigmentation. While their outdoor lifestyles still permitted sufficient cutaneous vitamin D3 (VD3) synthesis, their marginal nutritional status, coupled with cold-induced caloric needs, selected for moderate pigment reductions that diverted limited nutritional resources towards more urgent priorities (=metabolic conservation). The further pigment-dilution that evolved as humans reached north-central Europe (i.e., northern France, Germany), likely facilitated cutaneous VD3 synthesis, while also supporting ongoing, nutritional requirements. But at still higher European latitudes where little UV-B breaches the atmosphere (i.e., present-day UK, Scandinavia, Baltic States), pigment dilution alone could not suffice. There, other nonpigment-related mutations evolved to facilitate VD3 production; for example, in the epidermal protein, filaggrin, resulting in reduced levels of its distal metabolite, trans-urocanic acid, a potent UV-B chromophore. Thus, changes in human pigmentation reflect a complex interplay between latitude, climate, diet, lifestyle, and shifting metabolic priorities.

The effect of epidermal levels of urocanic acid on 25-hydroxyvitamin D synthesis and inflammatory mediators upon narrowband UVB irradiation.

BACKGROUND/PURPOSE: Urocanic acid (UCA) absorbs ultraviolet (UV)B radiation in the epidermis which may interfere with phototherapy. Therefore, the influence of individual levels of UCA on immune reactivity and vitamin D synthesis induced by narrowband UVB radiation was assessed. METHODS: Twenty-eight subjects with irritant contact dermatitis of the hands were irradiated with suberythemal doses of narrowband UVB radiation on their unaffected lower forearms on three consecutive days. Stratum corneum tape strips and epidermal interstitial fluid (ISF) as well as blood samples were analyzed. RESULTS: Narrowband UVB irradiation led to the conversion of trans-UCA into its cis-isomer in the epidermis. The observed increase in 25-hydroxyvitamin D serum concentrations was inversely correlated with the baseline levels of trans-UCA. Furthermore, UVB irradiation induced significant changes in the levels of CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP-1ß, and the IL-1RA/IL-1α ratio. The levels of IL-1α and CXCL9/MIG showed a trend toward increase. The changes in the levels of inflammatory and immunomodulatory mediators did not depend on baseline levels of trans-UCA. CONCLUSION: The results suggest that epidermal levels of trans-UCA affect vitamin D synthesis, but not cutaneous immune reactivity upon repeated exposure to suberythemal doses of narrowband UVB radiation. However, this requires further exploration.

Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation.

Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm²), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation.

Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis.

The epidermis protects human subjects from exogenous stressors and helps to maintain internal fluid and electrolyte homeostasis. Filaggrin is a crucial epidermal protein that is important for the formation of the corneocyte, as well as the generation of its intracellular metabolites, which contribute to stratum corneum hydration and pH. The levels of filaggrin and its degradation products are influenced not only by the filaggrin genotype but also by inflammation and exogenous stressors. Pertinently, filaggrin deficiency is observed in patients with atopic dermatitis regardless of filaggrin mutation status, suggesting that the absence of filaggrin is a key factor in the pathogenesis of this skin condition. In this article we review the various causes of low filaggrin levels, centralizing the functional and morphologic role of a deficiency in filaggrin, its metabolites, or both in the etiopathogenesis of atopic dermatitis.

Cell death by cornification.

Epidermal keratinocytes undergo a unique form of terminal differentiation and programmed cell death known as cornification. Cornification leads to the formation of the outermost skin barrier, i.e. the cornified layer, as well as to the formation of hair and nails. Different genes are expressed in coordinated waves to provide the structural and regulatory components of cornification. Differentiation-associated keratin intermediate filaments form a complex scaffold accumulating in the cytoplasm and, upon removal of cell organelles, fill the entire cell interior mainly to provide mechanical strength. In addition, a defined set of proteins is cross-linked by transglutamination in the cell periphery to form the so-called cornified envelope. Extracellular modifications include degradation of the tight linkages between corneocytes by excreted proteases, which allows corneocyte shedding by desquamation, and stacking and modification of the excreted lipids that fill the intercellular spaces between corneocytes to provide a water-repellant barrier. In hard skin appendages such as hair and nails these tight intercorneocyte connections remain permanent. Various lines of evidence exist for a role of organelle disintegration, proteases, nucleases, and transglutaminases contributing to the actual cell death event. However, many mechanistic aspects of kearatinocyte death during cornification remain elusive. Importantly, it has recently become clear that keratinocytes activate anti-apoptotic and anti-necroptotic pathways to prevent premature cell death during terminal differentiation. This review gives an overview of the current concept of cornification as a mode of programmed cell death and the anti-cell death mechanisms in the epidermis that secure epidermal homeostasis. This article is part of a Special Section entitled: Cell Death Pathways.

Positive and ecobiological contribution in skin photoprotection of ectoine and mannitol combined in vivo with UV filters.

BACKGROUND: Chronic exposure to ultraviolet (UV) irradiation causes immunosuppression, photoaging, and carcinogenesis by induction of a cascade of skin damages. Sunscreens currently on the market are not absorbing UV rays uniformly throughout the full UV range, high sun protection factor (SPF) sunscreens absorb most of UVB rays but are less effective in absorbing the UVA part of the spectrum. In the context, one approach could consist of preserving the skin natural resources and mechanisms, which is the foundation of the ecobiological approach, by combing UV filters and antioxidants to enhance their photoprotective effect. METHODS: First, the photoprotection properties of ectoine and mannitol association were characterized by the quantification of glutathione, reactive oxygen species, and double-stranded DNA breaks and by the epidermal Langerhans cells functionality. Second, the protection of squalene oxidation, catalase activity, and trans-urocanic acid (UCA) by the ectoine and mannitol association combined or not with SPF30 UV filters was assessed in vivo via non-invasive skin samplings in 10 subjects on irradiated areas. RESULTS: Using in vitro irradiated skin cell models, we demonstrated that this association significantly preserved intracellular glutathione levels, reduced DNA strand breaks induced by oxidative stress, and maintained Langerhans cell functionality. In vivo this association combined with UV filters presented significantly higher protection of three natural defense systems altered by UV compared to UV filters alone: squalene oxidation, catalase activity, and preservation of trans-UCA. CONCLUSION: This study demonstrates the ecobiological potential of combining UV filters with biological protection to increase skin photoprotection provided by specific active ingredients with antioxidative and immunosuppressive properties.

Galectin-7, induced by cis-urocanic acid and ultraviolet B irradiation, down-modulates cytokine production by T lymphocytes.

Urocanic acid (UCA) is an epidermal chromophore that undergoes trans to cis isomerization after UVB irradiation. cis-UCA is a potent inhibitor of cutaneous acquired immunity. The aim of this study was to explore the genes, which are upregulated by cis-UCA in normal human epidermal keratinocytes (NHEK) and investigated its role in vitro using human T-lymphocyte cell line, Jurkat cells. DNA microarray analysis and real-time PCR investigation revealed that cis-UCA, not trans-UCA, increased the expression of a gene encoding a ß-galactoside-binding lectin, galectin-7, LGALS7B. Immunohistochemical study demonstrated that galectin-7 was highly expressed in the epidermis in the patients with actinic keratosis. Galectin-7 administration upregulated apoptosis and inhibited the expression of interleukin-2 (IL2) and interferon-γ (IFNG) mRNA in Jurkat cells. Taken together, galectin-7 may play important roles in downregulating the functions of T lymphocytes after UVB irradiation and can be developed into novel immunosuppressive therapies for inflammatory skin diseases.

Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents.

The acute and chronic consequences of ultraviolet radiation on human skin are reviewed. An awareness of variations in naturally occurring photoprotective agents and the use of glass, sunglasses, and fabric can lead to effective protection from the deleterious effects of ultraviolet radiation. New systemic agents, including Polypodium leucotomos, afamelanotide, and antioxidants have potential as photoprotective agents.

Effect of an Emollient Emulsion Containing 15.0% of Caprylic/Capric Triglyceride on the Urocanic Acid of the Stratum Corneum.

Natural moisturizing factor (NMF) includes several compounds in the stratum corneum (SC), among them, urocanic acid (UCA). Ultraviolet (UV) exposure turns the trans-UCA of the SC into its cis isomer. We investigated the impact of a topical emollient emulsion treatment on the UCA isomers of the SC exposed to artificial UV stress. Aliquots of emollient emulsion were applied in healthy subjects for 2 h on delimited areas of the volar forearm, then, the SC was removed by tape stripping. Tapes were irradiated in a solar simulator chamber and a high performance liquid chromatograph was used to quantify UCA isomers from stripped SC extract. The amount of both UCA isomers were almost twice higher in the SC treated with the emollient emulsion. We also observed that the UV irradiation elevated the amount of the cis/trans UCA ratio on the SC (non-treated and treated), suggesting that the emollient sample was not able to avoid the UCA isomerization. The in vivo tests corroborated with the UCA data obtained ex vivo, since we found an increase in the superficial skin hydration with respective reduction of the TEWL, probably occurring by the occlusion performed by the emollient emulsion containing 15.0% w/w of caprylic/capric triglyceride.