Lipopeptide 78 from Staphylococcus epidermidis Activates b-Catenin To Inhibit Skin Inflammation

The appropriate inflammatory response is essential for normal wound repair, and skin commensal Staphylococcus epidermidis has been shown to regulate TLR3-mediated inflammatory response to maintain skin homeostasis after injury. However, the underlying mechanism by which S. epidermidis regulates wound-induced inflammation remains largely unexplored. In this study we identified a previously unknown lipopeptide 78 (LP78) from S. epidermidis and showed that LP78 inhibited TLR3-mediated skin inflammation to promote wound healing. Skin injury activated TLR3/NF-kB to promote the interaction of p65 and PPARg in nuclei and then initiated the inflammatory response in keratinocytes. LP78 activated TLR2-SRC to induce b-catenin phosphorylation at Tyr ⁶⁵⁴ . The phospho–b-catenin translocated into nuclei to bind to PPARg, thus disrupting the interaction between p65 and PPARg. The disassociation between p65 and PPARg reduced the expression of TLR3-induced inflammatory cytokines in skin wounds of normal and diabetic mice, which correlated with accelerated wound healing. Our data demonstrate that S. epidermidis–derived LP78 inhibits skin inflammation to promote wound healing and suggest that LP78 might be a potential compound for the treatment of delayed or unhealed wounds.