Lipopeptide 78 from Staphylococcus epidermidis Activates β-Catenin To Inhibit Skin Inflammation
Lipopeptide 78 from Staphylococcus epidermidis Activates β-Catenin To Inhibit Skin Inflammation
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来自表皮葡萄球菌的脂肽 78 激活 β-连环蛋白以抑制皮肤炎症。
DOI：
10.4049/jimmunol.1800813
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发表时间：
2019-02-15
影响因子：
4.4
通讯作者：
Lai, Yuping
中科院分区：
文献类型：
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作者：
Li, Dongqing;Wang, Wang;Lai, Yuping
适当的炎症反应对于正常的伤口修复是必不可少的，并且皮肤表皮葡萄球菌已经显示出调节TLR 3介导的炎症反应以维持损伤后的皮肤稳态。然而，S.表皮细胞调节伤口诱导的炎症仍然在很大程度上未被探索。在这项研究中，我们确定了一个以前未知的脂肽78（LP 78）从S。在表皮中进行的研究表明，LP 78抑制TLR 3介导的皮肤炎症以促进伤口愈合。皮肤损伤激活TLR 3/NF-κ B，促进p65和PPAR γ在细胞核内的相互作用，进而引发角质形成细胞的炎症反应。LP 78激活TLR 2-SRC以诱导Tyr 654处的β-连环蛋白磷酸化。磷酸-β-连环蛋白易位到细胞核中与PPAR γ结合，从而破坏p65和PPAR γ之间的相互作用。在正常和糖尿病小鼠的皮肤伤口中，p65和PPARg之间的分离减少了TLR 3诱导的炎性细胞因子的表达，这与加速伤口愈合相关。我们的数据表明，S。表皮衍生的LP 78抑制皮肤炎症以促进伤口愈合，并表明LP 78可能是用于治疗延迟或未愈合伤口的潜在化合物。
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-kappa B to promote the interaction of p65 and PPAR gamma 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 PPAR gamma, thus disrupting the interaction between p65 and PPAR gamma. 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.