title: Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.
abstract: BACKGROUND
  Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD.
  
  
  OBJECTIVE
  This study elucidates the mode of action of topical BM and pimecrolimus cream in AD.
  
  
  METHODS
  Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis.
  
  
  RESULTS
  Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment.
  
  
  CONCLUSIONS
  The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.
authors.affiliation: Department of Dermatology, University of Kiel, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Jensen
authors.forename: A
authors.initials: A
authors.lastname: Scherer
authors.forename: C
authors.initials: C
authors.lastname: Wanke
authors.forename: M
authors.initials: M
authors.lastname: Bräutigam
authors.forename: S
authors.initials: S
authors.lastname: Bongiovanni
authors.forename: M
authors.initials: M
authors.lastname: Letzkus
authors.forename: F
authors.initials: F
authors.lastname: Staedtler
authors.forename: J
authors.initials: J
authors.lastname: Kehren
authors.forename: M
authors.initials: M
authors.lastname: Zuehlsdorf
authors.forename: T
authors.initials: T
authors.lastname: Schwarz
authors.forename: M
authors.initials: M
authors.lastname: Weichenthal
authors.forename: R
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: E
authors.initials: E
authors.lastname: Proksch
mesh_terms: D000328:Adult; D001623:Betamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D019703:Calcineurin / Q000494:pharmacology / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002463:Cell Membrane Permeability / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D000091344:Filaggrin Proteins; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005938:Glucocorticoids; D011506:Proteins; C117268:pimecrolimus; D001623:Betamethasone; D019703:Calcineurin; D016559:Tacrolimus