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Series GSE32473 Query DataSets for GSE32473
Status Public on Sep 30, 2011
Title Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Topical corticosteroids and calcineurin inhibitors are well known treatments of atopic dermatitis (AD), but differ in their efficacy and side effects. A study in AD patients has demonstrated that betamethasone valerate (BM) though clinically more efficient impaired skin barrier repair in contrast to pimecrolimus. Objective: The present study elucidates the mode of action of topical BM and pimecrolimus cream in AD.
Methods: These two components were subjected to gene expression profile analysis in lesional AD skin after topical treatment.
Results: BM resulted in a significant reduction of mRNA levels of genes encoding for markers for 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.
Conclusion: The gene expression profiles are consistent with previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Hence, this study confirms the hypothesis at the molecular level that corticosteroids are a suitable treatment for acutely exacerbated AD, but that pimecrolimus is preferable for long-term treatment and stabilization.
Overall design Fifteen patients with mild-to-moderate AD (according to Hanifin and Rajka criteria) and a target lesion score (pEASI) of 3 to 8 (on a scale of 0-12) for both right and left target lesions, and symmetric AD lesions (not differing >1 point between the right and left sides) affecting the upper limbs by at least 10% were treated twice daily for 3 weeks on 1 upper limb with 1% pimecrolimus cream and on the other upper limb with 0.1% betamethasone valerate cream in a double blind manner. The clinical, biophysical, immuno-histological and electron-microscopical results have already been published. Biopsy samples have been obtained before and after the end of the treatments for gene expression profiling measurement from ten patients out of the group of 15. Of the ten patients there were seven women and three men. The average age was 23.8 ± 3.6 years. After three weeks of treatment with pimecrolimus and BM cream, the clinical score (pEASI) revealed a reduction of 0.9 ± 2.1 and 2.9 ± 3.1, respectively. The study was approved by the local ethics commission and the German Federal Institute for Pharmaceuticals and Medical Products (EudraCT-Nr. 2004-004824-11).
Contributor(s) Jensen JM, Scherer A, Wanke C, Braeutigam M, Bongiovanni S, Letzkus M, Staedtler F, Kehren J, Zuehlsdorf M, Schwarz T, Weichenthal M, Foelster-Holst R, Proksch E
Citation(s) 22142306
Submission date Sep 29, 2011
Last update date Mar 25, 2019
Contact name Andreas Scherer
Organization name Spheromics
Street address Pajutie 3A
City Kontiolahti
ZIP/Postal code 81100
Country Finland
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (30)
GSM803585 patient 6, arm treated with betamethasone
GSM803586 patient 6, baseline
GSM803587 patient 6, arm treated with pimecrolimus
BioProject PRJNA147695

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Supplementary file Size Download File type/resource
GSE32473_RAW.tar 131.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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