title: The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions.
abstract: The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under consideration. Thus far, we have evidence of its anti-inflammatory and immunomodulatory activity, and recent papers focus on its effect on epidermal barrier function. This study analysed changes in the expression of genes associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions after 2 weeks of exposure to PIM 1% cream. A real-time quantitative PCR analysis of selected epidermal differentiation complex genes and three alternative pathway keratins was performed in skin biopsies from 11 individuals with AD before and after PIM exposure. The real-time quantitative PCR analysis was compared to non-lesional skin in the same patients. Involucrin, a small proline-rich region (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over-expression in lesional skin followed by significant decrease after PIM therapy. The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the decrease after PIM treatment was not significant. The changes in S100 A2, A7 and A8 followed a similar course with borderline significance. SPRR4 had a significant decrease in expression in lesional versus non-lesional skin, which persisted after PIM treatment. No significant changes were detected in mRNA expression levels of filaggrin and loricrin. Our results suggest that PIM can be effective in restoring the epidermal barrier in patients with AD at least in part by its impact on expression of genes, which are important for the normal barrier function of skin.
authors.affiliation: Clinical Department of Internal Diseases, Dermatology and Allergology in Zabrze, Medical University of Silesia, Katowice, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Grzanka
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Zebracka-Gala
authors.forename: Regina
authors.initials: R
authors.lastname: Rachowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bozek
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kowalska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jarzab
mesh_terms: D000328:Adult; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D053536:Keratin-16 / Q000235:genetics / Q000378:metabolism; D053553:Keratin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009824:Ointments; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D003879:Dermatologic Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D053536:Keratin-16; D053553:Keratin-6; D009824:Ointments; D011498:Protein Precursors; D012333:RNA, Messenger; C524531:SPRR1A protein, human; C444462:SPRR4 protein, human; C032253:involucrin; C117268:pimecrolimus; D016559:Tacrolimus