PuSH - Publication Server of Helmholtz Zentrum München: TNF receptor I on human keratinocytes is a binding partner for staphylococcal protein A resulting in the activation of NF kappa B, AP-1, and downstream gene transcription.

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Classen, A.* ; Kalali, B.N.* ; Schnopp, C.* ; Andres, C.* ; Aguilar-Pimentel, J.A. ; Ring, J.* ; Ollert, M.* ; Mempel, M.

TNF receptor I on human keratinocytes is a binding partner for staphylococcal protein A resulting in the activation of NF kappa B, AP-1, and downstream gene transcription.

Exp. Dermatol. 20, 48-52 (2011)

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Open Access Green as soon as Postprint is submitted to ZB.

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Primary human keratinocytes and immortalized HaCaT cells were analysed for their capacity to bind purified staphylococcal protein A (SpA). Co-incubation with FITC-labelled SpA led to a dose-depending attachment. Pull-down experiments with cellular extracts revealed the TNFα receptor I (TNF RI) as binding partner on keratinocytes. Thus, we next looked for expression of this receptor in human epidermis and cultured keratinocytes. TNF RI is strongly expressed on all keratinocytes analysed, both at the mRNA and protein level and activation by SpA at optimal doses of 50-100 μg/ml resulted in the phosphorylation of the TNF RI downstream kinases MEK1/2, JNK1/2, and p38 subsequently leading to translocation of the p65 NF kappa B subunit and AP-1 into the nucleus. This translocation was then followed by increased expression of IL-8 and COX-2, two known NF kappa B-induced pro-inflammatory genes. To further test the relevance of our findings, we analysed in vitro production of over 100 strains isolated from atopic eczema showing that more than 85% of the tested strains produced extracellular SpA in substantial amounts. Thus, besides superantigens, haemolysins, and other cell wall components, Staphylococcus aureus exerts pro-inflammatory stimuli on human keratinocytes through the production of SpA signalling through TNF RI.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Keratinocytes; Protein A; Staphylococcus aureus; TNF RI

ISSN (print) / ISBN 0906-6705

e-ISSN 1600-0625

Journal Experimental Dermatology

Quellenangaben Volume: 20, Issue: 1, Pages: 48-52

Publisher Wiley

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)