IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion

• Published in: Experimental dermatology Vol. 21; no. 2; pp. 104 - 110
• Main Authors: Gutowska-Owsiak, Danuta, Schaupp, Anna L., Salimi, Maryam, Selvakumar, Tharini A., McPherson, Tess, Taylor, Stephen, Ogg, Graham S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Blackwell
• Subjects: Allergic diseases; atopic eczema; Biological and medical sciences; Cadherins - genetics; Cadherins - metabolism; Calpain - genetics; Cathepsin B - genetics; Cathepsin D - genetics; Cathepsin L - genetics; Cell Adhesion Molecules - genetics; Cell Differentiation - genetics; Cell Line; Cells, Cultured; Claudins - genetics; Cytoskeletal Proteins - genetics; Dermatology; Down-Regulation - genetics; epidermal barrier; filaggrin; gamma Catenin - genetics; gamma Catenin - metabolism; Gene Expression - drug effects; Gene Expression - genetics; Humans; IL-17; Immunopathology; Interleukin-17 - pharmacology; Intermediate Filament Proteins - genetics; Intermediate Filament Proteins - metabolism; keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Phosphoproteins - genetics; Phosphoproteins - metabolism; S100 Proteins - genetics; Skin allergic diseases. Stinging insect allergies; Up-Regulation - genetics; Zonula Occludens-1 Protein; Zonula Occludens-2 Protein; Allergy; Immunopathology; Skin disease; Dermatology; keratinocytes; Adhesion; atopic eczema; Interleukin 17; Atopy; Eczema; IL-17; Keratinocyte; epidermal barrier; filaggrin
• DOI: 10.1111/j.1600-0625.2011.01412.x
• ISSN: 0906-6705

:  Atopic eczema and psoriasis are common skin diseases. While it is well established that the pathogenesis of these diseases varies, both are characterized by impairment in epidermal barrier function and abnormal IL‐17 expression in the skin and peripheral blood. Recent findings indicated that filaggrin is essential during barrier formation and its insufficiency underlies the pathogenesis of atopic eczema. Filaggrin downregulation has also been reported in psoriasis. It is clear that Th1/Th2 bias influences expression of the protein, but an analysis of the effects of interleukin‐17 (IL‐17) on the expression of the protein and profilaggrin‐processing enzymes has not yet been reported. In addition, the effect of the cytokine on components of functional epidermal barrier, tight junctions and adhesion/desmosomal proteins, has not been elucidated. Keratinocytes were exposed to interleukin‐17A, and microarray analysis was performed. Filaggrin protein level was assessed by western blot. We have observed a significant decrease in profilaggrin mRNA level in interleukin‐17A‐exposed cultures (P = 0.008). Expression of processing enzymes was also altered, indicating an indirect effect of the cytokine on filaggrin production/degradation. Moreover, expression of many genes involved in cellular adhesion was also decreased. A significant downregulation of filaggrin at the protein level was detected by western blot in immortal and primary keratinocytes. Gene ontology analysis indicated changes in keratinization, epidermal differentiation and formation of the cornified envelope. We conclude that IL‐17A downregulates the expression of filaggrin and genes important for cellular adhesion which could affect epidermal barrier formation. This effect potentially contributes to barrier dysfunction and could become a possible therapeutic target.