Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients.
In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn's disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2409155?pdf=render |
| _version_ | 1818363374885404672 |
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| author | Patrick L J M Zeeuwen Gys J de Jongh Diana Rodijk-Olthuis Marijke Kamsteeg Renate M Verhoosel Michelle M van Rossum Pieter S Hiemstra Joost Schalkwijk |
| author_facet | Patrick L J M Zeeuwen Gys J de Jongh Diana Rodijk-Olthuis Marijke Kamsteeg Renate M Verhoosel Michelle M van Rossum Pieter S Hiemstra Joost Schalkwijk |
| author_sort | Patrick L J M Zeeuwen |
| collection | DOAJ |
| description | In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn's disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease. |
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| id | doaj.art-3a890d0f22654e63b80a26295f97a3b9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:47:28Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3a890d0f22654e63b80a26295f97a3b92022-12-21T23:30:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0136e230110.1371/journal.pone.0002301Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients.Patrick L J M ZeeuwenGys J de JonghDiana Rodijk-OlthuisMarijke KamsteegRenate M VerhooselMichelle M van RossumPieter S HiemstraJoost SchalkwijkIn the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn's disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease.http://europepmc.org/articles/PMC2409155?pdf=render |
| spellingShingle | Patrick L J M Zeeuwen Gys J de Jongh Diana Rodijk-Olthuis Marijke Kamsteeg Renate M Verhoosel Michelle M van Rossum Pieter S Hiemstra Joost Schalkwijk Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. PLoS ONE |
| title | Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. |
| title_full | Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. |
| title_fullStr | Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. |
| title_full_unstemmed | Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. |
| title_short | Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients. |
| title_sort | genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients |
| url | http://europepmc.org/articles/PMC2409155?pdf=render |
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