Omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) are nowadays desirable components of oils with special dietary and functional properties. Their therapeutic and health-promoting effects have already been established in various chronic inflammatory and autoimmune diseases through various mechanisms, including modifications in cell membrane lipid composition, gene expression, cellular metabolism, and signal transduction. The application of ω-3 and ω-6 PUFAs in most common skin diseases has been examined in numerous studies, but their results and conclusions were mostly opposing and inconclusive. It seems that combined ω-6, gamma-linolenic acid (GLA), and ω-3 long-chain PUFAs supplementation exhibits the highest potential in diminishing inflammatory processes, which could be beneficial for the management of inflammatory skin diseases, such as atopic dermatitis, psoriasis, and acne. Due to significant population and individually-based genetic variations that impact PUFAs metabolism and associated metabolites, gene expression, and subsequent inflammatory responses, at this point, we could not recommend strict dietary and supplementation strategies for disease prevention and treatment that will be appropriate for all. Well-balanced nutrition and additional anti-inflammatory PUFA-based supplementation should be encouraged in a targeted manner for individuals in need to provide better management of skin diseases but, most importantly, to maintain and improve overall skin health.
Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18–0.61), 0.56 (IQR 0.32–0.76) and 19.32 (IQR 7.86–27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = −0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes.
Background Atopic dermatitis (AD) presents with the wide spectrum of clinical phenotypes within and between various populations. Recent study showed low frequency of filaggrin loss-of-function (FLG LOF) mutations in Croatian AD patients. At present, there are no data on biomarkers of immune response in Croatian AD patients that might be useful in the selection and monitoring of novel immune therapies. Objectives To investigate levels of cytokines of various signature in the stratum corneum (SC) collected from lesional and non-lesional skin of AD patients and healthy controls and to evaluate their relationship with the severity of disease and skin barrier function.Methods SC samples were collected from 100 adult patients with moderate-to-severe AD and 50 healthy controls. The levels of 21 cytokines were measured by multiplex immunoassay. We conducted machine learning analysis to assess whether a small number of cytokine measurements can discriminate between healthy controls and AD patients and can predict AD severity (SCORAD). ResultsThe SC levels of thirteen cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 immune response showed significant differences between healthy and AD skin. Our analysis demonstrated that as few as three cytokines measured in lesional skin can discriminate healthy controls and AD with an accuracy of 99% and that the predictive models for SCORAD did not achieve a high accuracy. Cytokine levels were highly correlated with the levels of filaggrin degradation products and skin barrier function.Conclusions Stratum corneum analysis revealed aberrant levels of cytokines representing innate immunity, Th-1-, Th-2-and Th-17/22-mediated immune response in Croatian AD patients. Increased Th-2 cytokines and their strong association with natural moisturizing factor (NMF) can explain low NMF levels despite of low frequency of FLG LOF mutations in Croatian population. Predictive models for SCORAD identified cytokines associated with SCORAD but warrants further investigation.
Background FLG loss-of-function mutations (FLG LOF) represent the strongest genetic risk factor for atopic dermatitis (AD) and are associated with early-onset and more severe disease. The prevalence of FLG mutations varies greatly across Europe. At present, there are no data on FLG mutation prevalence in Croatian AD patients. Objectives To investigate the prevalence of FLG LOF mutations in adult patients with AD and healthy controls. Next to measure the stratum corneum (SC) levels of filaggrin degradation products (NMF), transepidermal water loss (TEWL) and pH in lesional and non-lesional skin. Methods We recruited 100 AD patients with moderate to severe disease and 50 healthy controls. They were screened for three FLG mutations (R501X, 2282del4 and R2447X). Samples of the SC for NMF analysis were collected by adhesive tapes. TEWL and skin surface pH levels were determined on the lesional and non-lesional skin. Results The combined mutation frequency was 4% in the AD group, and all patients with FLG mutations were homozygous carriers. In the control group, no mutations were found. The most common FLG mutation in AD patients was 2282del4 (3%), followed by R501X (1%). As compared to healthy controls, NMF values were strongly reduced in lesional skin; however, no significant difference was found for non-lesional skin. AD patients had elevated TEWL in both lesional and non-lesional skin. The same pattern was observed for pH. Conclusions Our study expands understanding of the landscape of FLG mutations in the European population. The low frequency of FLG mutations and similar levels of filaggrin degradation products in healthy controls and in non-lesional skin of AD patients suggest that filaggrin deficiency does not confer a major risk for AD in the Croatian population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.