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Rebane, A.* ; Zimmermann, M.* ; Aab, A.* ; Baurecht, H.* ; Koreck, A.* ; Karelson, M.* ; Abram, K.* ; Metsalu, T.* ; Pihlap, M.* ; Meyer, N.* ; Fölster-Holst, R.* ; Nagy, N.* ; Kemeny, L.* ; Kingo, K.* ; Vilo, J.* ; Illig, T. ; Akdis, M.* ; Franke, A.* ; Novak, N.* ; Weidinger, S.* ; Akdis, C.A.*

Mechanisms of IFN-γ-induced apoptosis of human skin keratinocytes in patients with atopic dermatitis.

J. Allergy Clin. Immunol. 129, 1297-1306 (2012)
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BACKGROUND: Enhanced apoptosis of keratinocytes is the main cause of eczema and spongiosis in patients with the common inflammatory skin disease atopic dermatitis (AD). OBJECTIVE: The aim of the study was to investigate molecular mechanisms of AD-related apoptosis of keratinocytes. METHODS: Primary keratinocytes isolated from patients with AD and healthy donors were used to study apoptosis by using annexin V/7-aminoactinomycin D staining. Illumina mRNA Expression BeadChips, quantitative RT-PCR, and immunofluorescence were used to study gene expression. In silico analysis of candidate genes was performed on genome-wide single nucleotide polymorphism data. RESULTS: We demonstrate that keratinocytes of patients with AD exhibit increased IFN-γ-induced apoptosis compared with keratinocytes from healthy subjects. Further mRNA expression analyses revealed differential expression of apoptosis-related genes in AD keratinocytes and skin and the upregulation of immune system-related genes in skin biopsy specimens of chronic AD lesions. Three apoptosis-related genes (NOD2, DUSP1, and ADM) and 8 genes overexpressed in AD skin lesions (CCDC109B, CCL5, CCL8, IFI35, LYN, RAB31, IFITM1, and IFITM2) were induced by IFN-γ in primary keratinocytes. The protein expression of IFITM1, CCL5, and CCL8 was verified in AD skin. In line with the functional studies and AD-related mRNA expression changes, in silico analysis of genome-wide single nucleotide polymorphism data revealed evidence of an association between AD and genetic markers close to or within the IFITM cluster or RAB31, DUSP1, and ADM genes. CONCLUSION: Our results demonstrate increased IFN-γ responses in skin of patients with AD and suggest involvement of multiple new apoptosis- and inflammation-related factors in the development of AD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cytokine; mRNA expression array; atopic eczema; inflammation; allergy; RECEPTOR EXPRESSION; ATONIC DERMATITIS; GENE-EXPRESSION; IN-SITU; ASSOCIATION; ECZEMA; CELLS; DISEASES; VARIANT; ABNORMALITIES
Sprache
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 129, Heft: 5, Seiten: 1297-1306 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Molecular Epidemiology (AME)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504200-001
PubMed ID 22445417
DOI 10.1016/j.jaci.2012.02.020
WOS ID 000303418000018
Scopus ID 84860436608
Erfassungsdatum 2012-06-06
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