The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill
Keyword(s):  
Ultraviolet Radiation ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Transepidermal Water Loss ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Positive Effects ◽  
Terrestrial Mammals ◽  
The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

scholarly journals Study of Skin Barrier Function in Psoriasis: The Impact of Emollients

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 651
Author(s):  
Daniel Maroto-Morales ◽  
Trinidad Montero-Vilchez ◽  
Salvador Arias-Santiago
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Epidermal Barrier ◽  
Stratum Corneum Hydration ◽  
Systemic Inflammatory Disease ◽  
Water Based ◽  
The Impact

Psoriasis is a chronic multi-systemic inflammatory disease that affects the epidermal barrier. Emollients can be used as a coadjutant therapy for psoriasis management, but little is known about how the epidermal barrier function in psoriatic patients is modified by moisturizers. The objective of this study is to evaluate the effect of Vaseline jelly and a water-based formula on epidermal barrier function in psoriatic patients. Thirty-one patients with plaque-type psoriasis and thirty-one gender and age-matched healthy controls were enrolled in the study. Temperature, transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH, elasticity and the erythema index were measured using non-invasive tools before and after applying Vaseline jelly and a water-based formula. TEWL was higher in psoriatic plaques than uninvolved psoriatic skin (13.23 vs. 8.54 g·m−2·h−1; p < 0.001). SCH was lower in psoriatic plaques than uninvolved psoriatic skin and healthy skin (13.44 vs. 30.55 vs. 30.90 arbitrary units (AU), p < 0.001). In psoriatic plaques, TEWL decreased by 5.59 g·m−2·h−1 (p = 0.001) after applying Vaseline Jelly, while it increased by 3.60 g·m−2·h−1 (p = 0.006) after applying the water-based formula. SCH increased by 9.44 AU after applying the water-based formula (p = 0.003). The use of emollients may improve epidermal barrier function in psoriatic patients. TEWL is decreased by using Vaseline, and SCH is increased by using the water-based formula.

scholarly journals PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubrey N. Michi ◽  
Bryan G. Yipp ◽  
Antoine Dufour ◽  
Fernando Lopes ◽  
David Proud
Keyword(s):  
Host Defense ◽  
Barrier Function ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

scholarly journals Hypoxia-inducible factor hydroxylase inhibition enhances the protective effects of cyclosporine in colitis

2019 ◽  
Vol 317 (2) ◽  
pp. G90-G97 ◽  
Author(s):  
Doug N. Halligan ◽  
Mohammed N. Khan ◽  
Eric Brown ◽  
Catherine R. Rowan ◽  
Ivan S. Coulter ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune System ◽  
Protective Effect ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Inflammatory bowel disease (IBD) is characterized by epithelial barrier dysfunction with resultant inflammation as the mucosal immune system becomes exposed to luminal antigens. The hydroxylase inhibitor dimethyloxalylglycine (DMOG) reduces symptoms in experimental colitis through the upregulation of genes promoting barrier function and inhibition of epithelial cell apoptosis. The immunosuppressive drug cyclosporine reduces inflammation associated with IBD via suppression of immune cell activation. Given the distinct barrier protective effect of DMOG and the anti-inflammatory properties of cyclosporine, we hypothesized that combining these drugs may provide an enhanced protective effect by targeting both barrier dysfunction and inflammation simultaneously. We used the dextran sulfate sodium model of colitis in C57BL/6 mice to determine the combinatorial efficacy of cyclosporine and DMOG. While cyclosporine and DMOG ameliorated disease progression, in combination they had an additive protective effect that surpassed the level of protection afforded by either drug alone. The ability of DMOG to augment the anti-inflammatory effects of cyclosporine was largely due to preservation of barrier function and at least in part due to zonula occludens-1 regulation. We propose that combining the barrier protective effects of a hydroxylase inhibitor with the anti-inflammatory effects of cyclosporine provides added therapeutic benefit in colitis. NEW & NOTEWORTHY Inflammatory bowel disease is the result of decreased intestinal epithelial barrier function leading to exposure of the mucosal immune system to luminal antigens causing inflammation, which in turn further decreases epithelial barrier function. We demonstrate for the first time that strengthening the epithelial barrier with a hydroxylase inhibitor in combination with the administration of the immunosuppressive cyclosporine provides additive therapeutic advantage in a murine model of colitis

scholarly journals Erythema Increase Predicts Psoriasis Improvement after Phototherapy

2021 ◽  
Vol 10 (17) ◽  
pp. 3897
Author(s):  
Trinidad Montero-Vilchez ◽  
Antonio Martinez-Lopez ◽  
Alvaro Sierra-Sanchez ◽  
Miguel Soler-Gongora ◽  
Eladio Jimenez-Mejias ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Barrier Function ◽  
Cost Effective ◽  
Severity Index ◽  
Transepidermal Water Loss ◽  
Psoriatic Skin ◽  
Predictive Values ◽  
Epidermal Barrier ◽  
Stratum Corneum Hydration ◽  
Plaque Type

Psoriasis is a major global health problem. There is a need to develop techniques to help physicians select the most appropriate cost-effective therapy for each patient. The main objectives of this study are (1) to evaluate changes in epidermal barrier function and skin homeostasis after phototherapy and (2) to explore potentially predictive values in epidermal barrier function and skin homeostasis to assess clinical improvement after fifteen sessions of phototherapy. A total of 76 subjects, 38 patients with plaque-type psoriasis and 38 gender- and age-matched healthy volunteers, were included in the study. Erythema, transepidermal water loss (TEWL), temperature, stratum corneum hydration (SCH), pH, sebum, and antioxidant capacity were measured before and after the first and fifteenth phototherapy session. Erythema (401.09 vs. 291.12 vs. 284.52 AU, p < 0.001) and TEWL (18.23 vs. 11.44 vs. 11.41 g·m−2·h−1, p < 0.001) were significantly higher at psoriatic plaques than in uninvolved psoriatic skin and healthy volunteers, respectively, while SCH was lower (9.71 vs. 44.64 vs. 40.00 AU, p < 0.001). After fifteen phototherapy sessions, TEWL (–5.19 g·m−2·h−1, p = 0.016) decreased while SCH (+7.01 AU, p = 0.013) and erythema (+30.82 AU, p = 0.083) increased at psoriatic plaques. An erythema increase exceeding 53.23 AU after the first phototherapy session, with a sensitivity of 71.4% and specificity of 84.2%, indicates that a patient may improve Psoriasis Area and Severity Index (PASI) by ≥3 points after fifteen phototherapy sessions. In conclusion, phototherapy improves epidermal barrier function in psoriatic patients and the erythema increase after one phototherapy session could help doctors select psoriasis patients who are more likely to respond to phototherapy.

scholarly journals Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation

2014 ◽  
Vol 306 (8) ◽  
pp. C745-C752 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Peter V. Usatyuk ◽  
Guoxiang Yuan ◽  
May M. Lee ◽  
Jayasri Nanduri ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intermittent Hypoxia ◽  
Map Kinases ◽  
Fiber Formation ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
The Impact ◽  
Junction Proteins

The objective of the present study was to determine the impact of simulated apnea with intermittent hypoxia (IH) on endothelial barrier function and assess the underlying mechanism(s). Experiments were performed on human lung microvascular endothelial cells exposed to IH-consisting alternating cycles of 1.5% O2 for 30s followed by 20% O2 for 5 min. IH decreased transendothelial electrical resistance (TEER) suggesting attenuated endothelial barrier function. The effect of IH on TEER was stimulus dependent and reversible after reoxygenation. IH-exposed cells exhibited stress fiber formation and redistribution of cortactin, vascular endothelial-cadherins, and zona occludens-1 junction proteins along with increased intercellular gaps at cell-cell boundaries. Extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) were phosphorylated in IH-exposed cells. Inhibiting either ERK or JNK prevented the IH-induced decrease in TEER and the reorganization of the cytoskeleton and junction proteins. IH increased reactive oxygen species (ROS) levels, and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride, a membrane-permeable antioxidant, prevented ERK and JNK phosphorylation as well as IH-induced changes in endothelial barrier function. These results demonstrate that IH via ROS-dependent activation of MAP kinases leads to reorganization of cytoskeleton and junction proteins resulting in endothelial barrier dysfunction.

scholarly journals Molecular Mechanism of Epidermal Barrier Dysfunction as Primary Abnormalities

2020 ◽  
Vol 21 (4) ◽  
pp. 1194 ◽  
Author(s):  
Ai-Young Lee
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Early Time ◽  
Skin Disorders ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Skin Lipids ◽  
Target Molecules ◽  
Differentiation And Proliferation

Epidermal barrier integrity could be influenced by various factors involved in epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids. Dysfunction of this barrier can cause skin disorders, including eczema. Inversely, eczema can also damage the epidermal barrier. These interactions through vicious cycles make the mechanism complicated in connection with other mechanisms, particularly immunologic responses. In this article, the molecular mechanisms concerning epidermal barrier abnormalities are reviewed in terms of the following categories: epidermal calcium gradients, filaggrin, cornified envelopes, desquamation, and skin lipids. Mechanisms linked to ichthyoses, atopic dermatitis without exacerbation or lesion, and early time of experimental irritation were included. On the other hand, the mechanism associated with epidermal barrier abnormalities resulting from preceding skin disorders was excluded. The molecular mechanism involved in epidermal barrier dysfunction has been mostly episodic. Some mechanisms have been identified in cultured cells or animal models. Nonetheless, research into the relationship between the causative molecules has been gradually increasing. Further evidence-based systematic data of target molecules and their interactions would probably be helpful for a better understanding of the molecular mechanism underlying the dysfunction of the epidermal barrier.

scholarly journals Oxyresveratrol protective effects against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation on porcine intestinal epithelial IPEC-J2 cells

2018 ◽  
Vol 1 ◽  
Author(s):  
Murphy L.Y. Wan ◽  
Ka Ho Ling ◽  
Hani El-Nezami ◽  
Mingfu Wang
Keyword(s):  
Bacterial Translocation ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Damage ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Significant Difference

Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Previous experiments in our laboratory have proven that polyphenols such as resveratrol (RES) may be effective in enhancing epithelial barrier function. Due to the structural similarity of oxyresveratrol (OXY) with RES, it was hypothesized that OXY could also protect against DON-induced intestinal damage. Accordingly, this study aimed to explore potential protective effects of OXY against DON-induced epithelial barrier dysfunction and bacterial translocation on IPEC-J2 cells, in comparison to resveratrol (RES).The results showed that OXY increased transepithelial electrical resistance (TEER) and reduced FD-4 diffusion, whereas DON reduced TEER and increased FD-4 diffusion in IPEC-J2 cells. On the other hand, OXY reduced FD-4 diffusion in DON-damaged cells but showed no significant difference in terms of TEER. Such protective effects coincided with the significantly reduced E. coli translocation in cells co-exposed to DON and OXY. Further mechanistic studies demonstrated that OXY protected against DON-induced barrier dysfunction by enhancing the expression of claudin-4 via mitogen-activated protein kinase(MAPK)-dependent pathways. Apparently, OXY worked through the same way as RES did, with results dovetailed nicely with anticipation. These results imply that OXY may share similar health benefits with RES by enhancing epithelial barrier functions and protecting against DON-induced intestinal damage.

РОЛЬ КОЖНОГО МИКРОБИОЦЕНОЗА В ДИСФУНКЦИИ ЭПИДЕРМАЛЬНОГО БАРЬЕРА И РАЗВИТИИ АТОПИЧЕСКОГО ДЕРМАТИТА У ДЕТЕЙ РАННЕГО ВОЗРАСТА ИЗ ГРУППЫ

2019 ◽  
Author(s):  
N.B. Migacheva
Keyword(s):  
At Risk ◽  
Significant Risk ◽  
Skin Barrier ◽  
Significant Risk Factor ◽  
Transepidermal Water Loss ◽  
Skin Microbiome ◽  
Children At Risk ◽  
Barrier Dysfunction ◽  
Epidermal Barrier

Обоснование. Нарушение кожного микробиоценоза и колонизация кожи S. aureus при атопическом дерматите (АтД) является широко распространенным феноменом и фактором, осложняющим течение заболевания. В настоящее время не вполне понятно, какую роль играет S. aureus в реализации АтД у детей из группы риска по развитию аллергических заболеваний. Цель. Изучение состава кожного микробиоценоза у детей раннего возраста из группы риска, а также роли S. aureus в дисфункции кожного барьера и реализации АтД. Материалы и методы. Проведен анализ 12-месячного наблюдения за 37 детьми из группы риска по развитию аллергических заболеваний, включающий общеклиническое обследование, проведение микробиологического исследования кожи в возрасте 1 и 6 мес и изучение функции эпидермального барьера путем определения показателя трансэпидермальной потери влаги (ТЭПВ) в возрасте 1 3 6 и 12 мес. В качестве исхода рассматривалось формирование АтД в течение периода наблюдения. Результаты. Частота выявления S. aureus на коже детей в возрасте 1 мес составила 45,9, в возрасте 6 мес - 29,7. Корреляционный анализ выявил ассоциацию между колонизацией кожи S. aureus и снижением показателей ТЭПВ (р0,004), а также частотой развития у них АтД (p0,001). Заключение. Обнаружение S. aureus в кожном микробиоценозе детей из группы риска ассоциировано с дисфункцией эпидермального барьера и является значимым фактором риска реализации у них АтД.Background. Colonization of skin with S. aureus in atopic dermatitis (AD) patients is a widespread phenomenon and a factor complicating the course of the disease. At present, it is not quite clear the role of S. aureus in the development of AD in children at risk. The aim of our study was to discribe the skin microbiome composition in young children at risk, as well as to investigate the role of S. aureus in skin barrier dysfunction and the development of AD. Material and methods. 12months follow-up study of 37 infants at risk has been performed. It included a general clinical examination, a microbiological investigation of skin microbiome (at 1 and 6 months), and investigation of epidermal barrier function by determining the transepidermal water loss (TEWL) at 1, 3, 6 and 12 months. Realization of AD during the observation period was considered as main outcome. Results. The prevalence of S. aureus colonization of infants aged 1 month was 45.9, at the age of 6 months - 29.7. Correlation analysis revealed an association between the skin colonization with S. aureus and a decrease of TEWL (p 0.004), as well as the cumulative incidence of AD (p 0.001). Conclusion. The detection of S. aureus as a part of skin microbiocenosis in AD infants at risk is associated with dysfunction of the epidermal barrier and is a significant risk factor for the AD development.

scholarly journals Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

2018 ◽  
Vol 45 (1) ◽  
pp. 343-355 ◽  
Author(s):  
Zhihua Liu ◽  
Yinghai Tian ◽  
Yanqiong Jiang ◽  
Shihua Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Conditional Knockout ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Entire Study ◽  
Intestinal Barrier Dysfunction

Background/Aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Results: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Conclusion: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

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