| First Author | Li D | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 4 | Pages | 1219-1228 |
| PubMed ID | 30642981 | Mgi Jnum | J:272923 |
| Mgi Id | MGI:6280792 | Doi | 10.4049/jimmunol.1800813 |
| Citation | Li D, et al. (2019) Lipopeptide 78 from Staphylococcus epidermidis Activates beta-Catenin To Inhibit Skin Inflammation. J Immunol 202(4):1219-1228 |
| abstractText | 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-kappaB to promote the interaction of p65 and PPARgamma in nuclei and then initiated the inflammatory response in keratinocytes. LP78 activated TLR2-SRC to induce beta-catenin phosphorylation at Tyr(654) The phospho-beta-catenin translocated into nuclei to bind to PPARgamma, thus disrupting the interaction between p65 and PPARgamma. The disassociation between p65 and PPARgamma 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. |
