TNF-like weak inducer of apoptosis (TWEAK) and TNF-⍺ cooperate in the induction of keratinocyte apoptosis - 10/08/11
, Andrea Koreck, MD b, Norbert Meyer, MD a, Tomasz Basinski, PhD a, g, Flurina Meiler, PhD a, Burgler Simone, PhD a, Stefan Woehrl, MD d, Katharina Moritz, MD d, Thomas Eiwegger, MD a, e, Peter Schmid-Grendelmeier, MD f, Lajos Kemeny, MD b, c, Cezmi A. Akdis, MD a, ⁎ 
Reprint requests: Cezmi A. Akdis, MD, and Maya Zimmermann, PhD, Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, 7270 Davos, Switzerland.Abstract |
Background |
Activation of skin keratinocytes followed by their apoptotic death leads to eczema and spongiosis formations in patients with atopic dermatitis (AD). TNF-like weak inducer of apoptosis (TWEAK) binds to its receptor, fibroblast growth factor-inducible 14 (Fn14), and controls many cellular activities, including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation.
Objective |
The aim of the study was to investigate the role of TWEAK and Fn14 in the formation of eczema in patients with AD.
Methods |
Primary keratinocytes were isolated from nonlesional skin from patients with AD and psoriasis and from normal skin of healthy donors. Apoptosis analysis was performed by using annexin V/7-aminoactinomycin D and terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling staining. The expression and regulation of TWEAK, TNF-⍺, Fn14, TNF receptor (TNFR) 1, and TNFR2 were measured by means of RT-PCR, flow cytometric analysis, and ELISA. TWEAK and Fn14 expression of lesional AD and psoriatic skin and normal control skin was analyzed by using immunohistochemistry and immunofluorescence.
Results |
TWEAK and TNF-⍺ cooperate in the induction of apoptosis in primary keratinocytes obtained from patients with AD, patients with psoriasis, and healthy subjects and in artificial skin equivalents. TNFR1 and Fn14 were the main receptors involved. TWEAK upregulates TNF-⍺ expression in primary keratinocytes, whereas TNF-⍺ did not affect the expression of TWEAK and its receptors. High TWEAK expression was observed in AD lesions but not in psoriatic lesions or normal skin. Fn14 was highly expressed in the lesional skin of patients with AD and patients with psoriasis and in healthy control skin.
Conclusion |
The high expression of TWEAK in lesional AD skin contributes to the difference in keratinocyte apoptosis and lesional formation between AD and psoriasis.
Le texte complet de cet article est disponible en PDF.Key words : Human primary keratinocytes, eczema formation, atopic dermatitis, psoriasis, TNF-⍺, TNF-like weak inducer of apoptosis, TNF receptors, Fn14, apoptosis
Abbreviations used : AD, Fn14, NF-κB, 7-AAD, TLRL, TNFR, TRAIL, Treg, TUNEL, TWEAK
Plan
| The authors’ laboratory is supported by Swiss National Science Foundation grant 32-118226, the Global Allergy Asthma European Network (GA2LEN), the Christine Kühne Center for Allergy Research and Education (CK-CARE), and the OTKA NK77434 and TAMOP 4.2.2-08/1 grants. |
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| Disclosure of potential conflict of interest: C. A. Akdis receives research support from Novartis, Stallergenes, the Swiss National Science Foundation, the Global Allergy and Asthma European Network, and the Christine Kuhne Center for Allergy Research; is a fellow and interest group member of the American Academy of Allergy, Asthma & Immunology; is vice president of the European Academy of Allergy and Clinical Immunology; and is an ex–committee member WP leader for GA2LEN. The rest of the authors have declared that they have no conflict of interest. |
Vol 127 - N° 1
P. 200 - janvier 2011 Retour au numéro
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