Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivo.
Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating beta-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPARalpha and PPARgamma exhibited reduced mRNA expression, while PPARbeta/delta and LXRbeta were unaltered. Epidermal lipoxygenase-3, which may generate PPARalpha agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier.
Department of Medical Sciences, Dermatology and Venereology, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden. hans.torma@medsci.uu.se
Hans
H
Törmä
Berit
B
Berne
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000328:Adult; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D001391:Azo Compounds / Q000378:metabolism; D004798:Enzymes / Q000235:genetics*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D005962:Glucosylceramidase / Q000235:genetics; D005964:Glucosyltransferases / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects*; D008084:Lipoxygenase / Q000235:genetics; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D057093:Orphan Nuclear Receptors / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D051102:Serine C-Palmitoyltransferase / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics; D055815:Young Adult
D001391:Azo Compounds; D004798:Enzymes; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D012967:Sodium Dodecyl Sulfate; D006903:Hydroxymethylglutaryl CoA Reductases; C511051:ALOXE3 protein, human; D008084:Lipoxygenase; C514086:ALOX12B protein, human; D001092:Arachidonate 12-Lipoxygenase; D051102:Serine C-Palmitoyltransferase; D064429:Fatty Acid Synthases; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase; D005962:Glucosylceramidase; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase; C011049:oil red O