Genetically programmed differences in epidermal host defense between psoriasis and atopic dermatitis patients

Autor: Michelle M. van Rossum, Diana Rodijk-Olthuis, Gys J. de Jongh, Pieter S. Hiemstra, Joost Schalkwijk, Marijke Kamsteeg, Patrick L.J.M. Zeeuwen, Renate M. Verhoosel
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Dermatology/Psoriasis and Other Inflammatory Diseases
Keratinocytes
Gene prediction
lcsh:Medicine
Enzyme-Linked Immunosorbent Assay
Dermatology
Disease
Biology
Polymerase Chain Reaction
Dermatitis
Atopic
Proinflammatory cytokine
Translational research [ONCOL 3]
Psoriasis
Gene expression
medicine
Humans
RNA
Messenger
lcsh:Science
Dermatology/Skin Infections
Genetics and Genomics/Genetics of Disease
Chronic inflammation and autoimmunity [UMCN 4.2]
Multidisciplinary
Innate immune system
Hereditary cancer and cancer-related syndromes [ONCOL 1]
Genetics and Genomics/Functional Genomics
lcsh:R
Genetics and Genomics/Gene Expression
Atopic dermatitis
medicine.disease
Pathogenesis and modulation of inflammation [N4i 1]
Genetics and Genomics/Disease Models
Immunology
Genetics and Genomics/Genetics of the Immune System
lcsh:Q
Epidermis
Functional genomics
Infection and autoimmunity [NCMLS 1]
Dermatology/Atopic Dermatitis and Other Forms of Eczema
Research Article
Immunity
infection and tissue repair [NCMLS 1]
Zdroj: PLoS ONE, Vol 3, Iss 6, p e2301 (2008)
PLoS One, 3, 6
PLoS ONE
PLoS One, 3
ISSN: 1932-6203
Popis: Contains fulltext : 70186.pdf (Publisher’s version ) (Open Access) 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.
Databáze: OpenAIRE
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