Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Abstract Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expressi...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2008-03, Vol.126 (3), p.332-337
Main Authors: Kim, Byung Eui, Leung, Donald Y.M, Boguniewicz, Mark, Howell, Michael D
Format: Article
Language:English
Subjects:
Adult
Allergic diseases
Allergy and Immunology
Animals
Atopic dermatitis
Biological and medical sciences
Cytokines - metabolism
Dermatitis, Atopic - metabolism
Down-Regulation
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunopathology
Involucrin
Keratinocytes - metabolism
Loricrin
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Transgenic
Protein Precursors - genetics
Protein Precursors - metabolism
Skin allergic diseases. Stinging insect allergies
STAT-6
STAT6 Transcription Factor - metabolism
Th2 Cells - metabolism
Th2 cytokines
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Summary:Abstract Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expression of LOR and IVL is significantly decreased in involved (LOR: p < 0.001; IVL: p < 0.001) and uninvolved (LOR: p < 0.001; IVL: p < 0.001) skin of AD subjects, as compared to skin from healthy subjects. Using primary keratinocytes, we further demonstrate the down-regulatory effect of IL-4 and IL-13 – which are over-expressed in the skin of AD patients – on LOR and IVL expression in keratinocytes. Additionally, skin biopsies from signal transducer and activator of transcription (STAT)-6 transgenic mice were deficient in the expression and production of LOR and IVL. This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2007.11.006