Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu
Autor: | B. Pavicic, Branka Marinović, Susan M. I. Goorden, Karen J. M. Ghauharali-van der Vlugt, Anamaria Balić, Ivone Jakasa, Ruzica Jurakic Toncic, Sanja Kezic, Kristina Zuzul, Mikela Petkovic, Suzana Ljubojevic Hadzavdic, Femke S. Stet |
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Přispěvatelé: | Laboratory Genetic Metabolic Diseases, Coronel Institute of Occupational Health, APH - Personalized Medicine, APH - Societal Participation & Health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male sphinganine medicine.medical_treatment atopic dermatitis biomarkers stratum corneum ceramides sphingosine lcsh:Chemistry 030207 dermatology & venereal diseases chemistry.chemical_compound 0302 clinical medicine Biomarkers / metabolism SCORAD lcsh:QH301-705.5 Spectroscopy medicine.diagnostic_test integumentary system General Medicine Atopic dermatitis Sphingosine / metabolism Dermatitis Atopic / metabolism Computer Science Applications Cytokine medicine.anatomical_structure Cytokines Dermatitis Atopic / pathology Female Adult Ceramide Catalysis Article Dermatitis Atopic Inorganic Chemistry 03 medical and health sciences Immune system medicine Stratum corneum Humans Physical and Theoretical Chemistry Molecular Biology Transepidermal water loss Sphingosine business.industry Organic Chemistry medicine.disease Sphingosine / analogs & derivatives 030104 developmental biology Cytokines / metabolism lcsh:Biology (General) lcsh:QD1-999 chemistry Ceramides / metabolism Immunology business |
Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 6 International journal of molecular sciences, 21(6):1958. Multidisciplinary Digital Publishing Institute (MDPI) International Journal of Molecular Sciences, Vol 21, Iss 6, p 1958 (2020) |
ISSN: | 1422-0067 1661-6596 |
Popis: | 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&ndash tandem mass spectrometry (LC&ndash 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&ndash 0.61), 0.56 (IQR 0.32&ndash 0.76) and 19.32 (IQR 7.86&ndash 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 = &minus 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. |
Databáze: | OpenAIRE |
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