title: Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis.
abstract: A defective permeability barrier leads to the penetration of environmental allergens into the skin and initiates immunological reactions and inflammation crucially involved in the pathogenesis of atopic dermatitis (AD). Decreased stratum corneum ceramide content may cause the defect in permeability barrier function consistently found in AD. Acid and neutral sphingomyelinase (A- and N-SMase) generate ceramides with structural and signal transduction functions in epidermal proliferation and differentiation. We determined epidermal SMase activities, DNA synthesis, involucrin, loricrin, filaggrin, and keratin expression in lesional and non-lesional skin of AD patients. We found decreased epidermal A-SMase activity in lesional and non-lesional skin, correlating with reduced stratum corneum ceramide content and disturbed barrier function. N-SMase activity was reduced in non-lesional skin and more significantly reduced in lesional skin, correlating with impaired expression of cornified envelope proteins and keratins, important for skin barrier function. Changes in involucrin, loricrin, filaggrin, keratin K 5 (basal) and K 16 (proliferation associated) were noticed in non-lesional and lesional skin, whereas changes in K 10 (suprabasal), K 6 (proliferation associated), and K 17 (inflammation associated) were found only in lesional skin. In summary, reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in AD.
authors.affiliation: Department of Dermatology, University of Kiel, Kiel, Germany.
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Jensen
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Anke
authors.initials: A
authors.lastname: Baranowsky
authors.forename: Michael
authors.initials: M
authors.lastname: Schunck
authors.forename: Supandi
authors.initials: S
authors.lastname: Winoto-Morbach
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schütze
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
mesh_terms: D015415:Biomarkers; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002518:Ceramides / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology*; D004817:Epidermis / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013379:Substrate Specificity; D014867:Water / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002518:Ceramides; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; C064554:loricrin; D014867:Water; C032253:involucrin; D007633:Keratins; D013108:Sphingomyelin Phosphodiesterase