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.
Törmä
Hans
H
Department of Medical Sciences, Dermatology and Venereology, Akademiska sjukhuset, SE-751 85 Uppsala, Sweden. hans.torma@medsci.uu.se
Berne
Berit
B
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