Content » Vol 99, Issue 2

Investigative Report

Staphylococcus epidermidis-induced Interleukin-1 Beta and Human Beta-defensin-2 Expression in Human Keratinocytes is Regulated by the Host Molecule A20 (TNFAIP3)

Maren Simanski, Anna-Sophie Erkens, Franziska Rademacher, Jürgen Harder
DOI: 10.2340/00015555-3073


Staphylococcus epidermidis is an abundant skin commensal capable of activating cutaneous defense responses, such as induction of cytokines and antimicrobial peptides. To permanently colonize human skin and prevent inflammation S. epidermidis needs to control the induction of host defense mediators. We report here that S. epidermidis induces expression of the host regulator protein A20 in human keratinocytes, thereby controlling expression and release of interleukin-1 beta. siRNA-mediated knockdown of A20 expression strongly enhanced the induction of interleukin-1 beta gene expression and protein release in keratinocytes stimulated with S. epidermidis. Furthermore, siRNA-mediated knockdown of A20 resulted in enhanced gene expression and secretion of the antimicrobial peptide human beta-defensin-2 in keratinocytes facing S. epidermidis. Mechanistically, A20 negatively controlled S. epidermidis-induced activation of the transcription factor NF-kappaB. Together, these data indicate that S. epidermidis exploits A20 to attenuate cutaneous defense responses, which may help S. epidermidis to persist on human skin.


The abundant skin commensal Staphylococcus epidermidis induces innate defense mediators, such as IL-1 beta and the antimicrobial peptide hBD-2 in keratinocytes. This study shows that an exaggerated production of these defense mediators is controlled by the parallel S. epidermidis-mediated induction of the host molecule A20. A20 is a known inhibitor of inflammatory signalling, and dysregulation of A20 may be associated with chronic inflammatory diseases, such as psoriasis. Induction of A20 may help S. epidermidis to persist as a commensal on human skin and to avoid an increased inflammatory scenario. Targeted induction of A20 may be useful to treat specific cutaneous inflammatory conditions.

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