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
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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