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

Anna Claßen, Behnam N. Kalali, Christina Schnopp, Christian Andres, Juan A. Aguilar-Pimentel, Johannes Ring, Markus Ollert, Martin Mempel*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)48-52
Number of pages5
JournalExperimental Dermatology
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Keywords

  • Keratinocytes
  • Protein A
  • Staphylococcus aureus
  • TNF RI

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