The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions

:  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 ge...

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Published in:Experimental dermatology 2012-03, Vol.21 (3), p.184-188
Main Authors: Grzanka, Alicja, Zebracka-Gala, Jadwiga, Rachowska, Regina, Bozek, Andrzej, Kowalska, Małgorzata, Jarzab, Jerzy
Format: Article
Language:English
Subjects:
Adult
Allergic diseases
atopic dermatitis
Biological and medical sciences
Cornified Envelope Proline-Rich Proteins - genetics
Cornified Envelope Proline-Rich Proteins - metabolism
Dermatitis, Atopic - drug therapy
Dermatitis, Atopic - genetics
Dermatitis, Atopic - physiopathology
Dermatologic Agents - pharmacology
Dermatologic Agents - therapeutic use
Dermatology
epidermal differentiation complex
Female
gene expression
Gene Expression - drug effects
Gene Expression Profiling
Humans
Immunopathology
Keratin-16 - genetics
Keratin-16 - metabolism
Keratin-6 - genetics
Keratin-6 - metabolism
Male
Medical sciences
Middle Aged
Ointments
pimecrolimus
Protein Precursors - genetics
Protein Precursors - metabolism
RNA, Messenger - metabolism
Skin - drug effects
Skin - metabolism
Skin allergic diseases. Stinging insect allergies
Tacrolimus - analogs & derivatives
Tacrolimus - pharmacology
Tacrolimus - therapeutic use
Treatment Outcome
Young Adult
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Summary::  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.
ISSN:0906-6705
1600-0625
DOI:10.1111/j.1600-0625.2011.01417.x