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

被引：124

作者：

Rebane, Ana ^{[1
,2
]}

Zimmermann, Maya ^{[1
]}

Aab, Alar ^{[1
]}

Baurecht, Hansjoerg ^{[3
]}

Koreck, Andrea ^{[4
]}

Karelson, Maire ^{[5
]}

Abram, Kristi ^{[5
]}

Metsalu, Tauno ^{[6
]}

Pihlap, Maire ^{[2
]}

Meyer, Norbert ^{[1
]}

Foelster-Holst, Regina ^{[3
]}

Nagy, Nikoletta ^{[4
,7
]}

Kemeny, Lajos ^{[4
,7
]}

Kingo, Kulli ^{[5
,8
]}

Vilo, Jaak ^{[6
]}

Illig, Thomas ^{[9
,10
]}

Akdis, Muebeccel ^{[1
]}

Franke, Andre ^{[11
]}

Novak, Natalija ^{[12
]}

Weidinger, Stephan ^{[3
]}

Akdis, Cezmi A. ^{[1
]}

机构：

[1] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, CH-7270 Davos, Switzerland

[2] Univ Tartu, Fac Med, Tartu, Estonia

[3] Univ Hosp Schleswig Holstein, Dept Dermatol, Campus Kiel, Germany

[4] Univ Szeged, Dept Dermatol & Allergol, Szeged, Hungary

[5] Tartu Univ Hosp, Dept Dermatol, Tartu, Estonia

[6] Univ Tartu, Inst Comp Sci, Tartu, Estonia

[7] Hungarian Acad Sci, Dermatol Res Grp, Szeged, Hungary

[8] Univ Tartu, Ctr Mol & Clin Med, Dept Physiol, Tartu, Estonia

[9] Helmholtz Zentrum Munich, Inst Epidemiol, Munich, Germany

[10] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany

[11] Univ Kiel, Inst Clin Mol Biol, D-24098 Kiel, Germany

[12] Univ Bonn, Dept Dermatol & Allergy, Bonn, Germany

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2012年 / 129卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

Cytokine; mRNA expression array; atopic eczema; inflammation; allergy; RECEPTOR EXPRESSION; ATONIC DERMATITIS; GENE-EXPRESSION; IN-SITU; ASSOCIATION; ECZEMA; CELLS; DISEASES; VARIANT; ABNORMALITIES;

D O I：

10.1016/j.jaci.2012.02.020

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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-gamma-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-gamma 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-g responses in skin of patients with AD and suggest involvement of multiple new apoptosis-and inflammation-related factors in the development of AD. (J Allergy Clin Immunol 2012;129:1297-306.)

引用

页码：1297 / 1306

页数：10

共 43 条

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