ABSTRACT
BACKGROUND: The barrier dysfunction in atopic dermatitis (AD) skin correlates with stratum corneum (SC) lipid abnormalities including reduction of global lipid content, shorter ceramide (CER) as well as free fatty acid (FFA) chain length and altered CER subclass levels. However, the underlying cause of these changes in lipid composition has not been fully investigated. AIM: We investigated whether the expression of CER and FFA biosynthesis enzymes are altered in AD skin compared with control skin and determine whether changes in enzyme expression can be related with changes in lipid composition. METHODS: In AD patients and controls the expression of enzymes involved in the biosynthesis of FFAs and CERs was analyzed in relation to the SC lipid composition. These enzymes include stearoyl CoA desaturase (SCD), elongase 1 (ELOVL1) and ELOVL6 involved in FFA synthesis and ß-glucocerebrosidase (GBA), acid-sphingomyelinase (aSmase), ceramide synthase 3 (CerS3) involved in CER synthesis. In TH2 treated human skin equivalents (AD HSEs) mimicking lesional AD skin, the mRNA expression of these enzymes was investigated. RESULTS: The results reveal an altered expression of SCD and ELOVL1 in AD lesional skin. This was accompanied by functional changes displayed by increased unsaturated FFAs (SCD) and reduced FFA C22-C28 (ELOVL1) in AD lesional skin. The expression of GBA, aSmase and CerS3 were also altered in lesional skin. The CER composition in AD lesional skin showed corresponding changes such as increased CER AS and NS (aSmase) and decreased esterified ω-hydroxy CERs (CerS3). In support of the results from AD skin, the AD HSEs showed reduced mRNA ELOVL1, GBA and a Smase levels. CONCLUSION: This study shows that alterations in the expression of key enzymes involved in SC lipid synthesis contribute to changes in the lipid composition in AD skin and inflammation may influence expression of these enzymes.
Subject(s)
Ceramides/metabolism , Dermatitis, Atopic/pathology , Epidermis/metabolism , Fatty Acids, Nonesterified/metabolism , Lipogenesis , Acetyltransferases/metabolism , Adult , Cells, Cultured , Ceramides/analysis , Ceramides/biosynthesis , Cytokines/immunology , Dermatitis, Atopic/immunology , Epidermal Cells , Epidermis/pathology , Fatty Acid Elongases , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/biosynthesis , Female , Glucosylceramidase/metabolism , Humans , Keratinocytes , Male , Sphingomyelin Phosphodiesterase/metabolism , Sphingosine N-Acyltransferase/metabolism , Stearoyl-CoA Desaturase/metabolism , Th2 Cells/metabolism , Young AdultABSTRACT
BACKGROUND: Skin cancer incidence is rising, placing a burden on healthcare systems worldwide. This problem may even be more extensive than expected, since registration of (pre)malignancies of the skin is poor. OBJECTIVE: To provide insight into the numbers of (pre)malignancies in patients with actinic keratosis (AK) or basal cell carcinoma (BCC) in 2 university and 2 general hospitals. METHODS: The types and numbers of previous tumours and of tumours during a two-year follow-up were collected from 574 patients. RESULTS: Mean time between the first diagnosed (pre)malignancy and time of inclusion was 6.6 years. Overall, 60% had multiple types of (pre)malignancies. In BCC patients, 61% had multiple BCCs, in patients with squamous cell carcinoma (SCC), 40% had multiple SCCs. The combination 'BCC and SCC' occurred in 10%, 'BCC and AK' in 47%, 'SCC and AK' in 14%. CONCLUSION: High numbers of patients with multiple (pre)malignancies were found in this patient population in university and general hospitals, which may well reflect the Dutch hospital population. We conclude that skin cancer patients are more extensively affected than was expected up till now. Consequently, the management of skin cancer may be in need of adaptation in near future and the question arises whether dermatologists have the capacity for providing care for all these patients.
