Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes.
BACKGROUND: The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Inte...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797092261806211072 |
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| author | Gutowska-Owsiak, D Schaupp, A Salimi, M Taylor, S Ogg, G |
| author_facet | Gutowska-Owsiak, D Schaupp, A Salimi, M Taylor, S Ogg, G |
| author_sort | Gutowska-Owsiak, D |
| collection | OXFORD |
| description | BACKGROUND: The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Interleukin (IL)-22 is upregulated in lesional AE tissue, but its effects on filaggrin expression and genes associated with epidermal function have not yet been comprehensively addressed. OBJECTIVES: To investigate the effects of IL-22 on expression of filaggrin and genes encoding proteins relevant to epidermal function. METHODS: Microarray analysis was performed on IL-22-stimulated HaCaT keratinocytes. Filaggrin protein level was assessed by an intracellular enzyme-linked immunosorbent assay (ELISA) and Western blot in HaCaT cells and the findings were validated in primary keratinocytes. RESULTS: Exposure to IL-22 cytokine resulted in a downregulation of profilaggrin mRNA expression in HaCaT keratinocytes. The expression of genes involved in enzymatic processing of profilaggrin as well as the generation of natural moisturizing factor was also altered. Furthermore, there was an upregulation of many transcripts encoding proteins of the S100 family. Profilaggrin/filaggrin downregulation was detected by intracellular ELISA and Western blot in HaCaT cells. The relevance to the primary setting was confirmed in primary keratinocytes by Western blot. CONCLUSIONS: IL-22 downregulates profilaggrin/filaggrin expression in keratinocytes at both mRNA and protein levels and affects genes relevant to epidermal function. This novel pathway may have relevance to the pathogenesis and treatment of atopic and other skin disease. |
| first_indexed | 2024-03-07T03:43:37Z |
| format | Journal article |
| id | oxford-uuid:beb65ef2-aa76-4985-83e5-e4d2a216a1fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:43:37Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:beb65ef2-aa76-4985-83e5-e4d2a216a1fb2022-03-27T05:41:49ZInterleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:beb65ef2-aa76-4985-83e5-e4d2a216a1fbEnglishSymplectic Elements at Oxford2011Gutowska-Owsiak, DSchaupp, ASalimi, MTaylor, SOgg, GBACKGROUND: The identification of filaggrin mutations has contributed towards our understanding of hereditary factors associated with epidermal dysfunction observed in individuals with atopic eczema (AE). However, factors that predispose to acquired filaggrin modulation are not well understood. Interleukin (IL)-22 is upregulated in lesional AE tissue, but its effects on filaggrin expression and genes associated with epidermal function have not yet been comprehensively addressed. OBJECTIVES: To investigate the effects of IL-22 on expression of filaggrin and genes encoding proteins relevant to epidermal function. METHODS: Microarray analysis was performed on IL-22-stimulated HaCaT keratinocytes. Filaggrin protein level was assessed by an intracellular enzyme-linked immunosorbent assay (ELISA) and Western blot in HaCaT cells and the findings were validated in primary keratinocytes. RESULTS: Exposure to IL-22 cytokine resulted in a downregulation of profilaggrin mRNA expression in HaCaT keratinocytes. The expression of genes involved in enzymatic processing of profilaggrin as well as the generation of natural moisturizing factor was also altered. Furthermore, there was an upregulation of many transcripts encoding proteins of the S100 family. Profilaggrin/filaggrin downregulation was detected by intracellular ELISA and Western blot in HaCaT cells. The relevance to the primary setting was confirmed in primary keratinocytes by Western blot. CONCLUSIONS: IL-22 downregulates profilaggrin/filaggrin expression in keratinocytes at both mRNA and protein levels and affects genes relevant to epidermal function. This novel pathway may have relevance to the pathogenesis and treatment of atopic and other skin disease. |
| spellingShingle | Gutowska-Owsiak, D Schaupp, A Salimi, M Taylor, S Ogg, G Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title | Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title_full | Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title_fullStr | Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title_full_unstemmed | Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title_short | Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. |
| title_sort | interleukin 22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes |
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