Lavender essential oil accelerates lipopolysaccharide-induced chronic wound healing by inhibiting caspase-11-mediated macrophage pyroptosis
Lavender essential oil accelerates lipopolysaccharide-induced chronic wound healing by inhibiting caspase-11-mediated macrophage pyroptosis
复制标题
薰衣草精油通过抑制 caspase-11 介导的巨噬细胞焦亡加速脂多糖诱导的慢性伤口愈合
DOI：
10.1002/kjm2.12654
复制
发表时间：
2023-02-06
影响因子：
3.3
通讯作者：
Guo, Wei
中科院分区：
文献类型：
--
作者：
Ao, Xiang;Yan, Huan;Guo, Wei
慢性伤口严重影响老年人、肥胖人群、糖尿病患者的生活质量。过度的炎症反应是延迟慢性伤口愈合的关键驱动因素。虽然熏衣草精油（EO [lav]）已被证明具有抗炎和加速伤口治疗的作用，但涉及的具体分子机制仍不明确。结果显示，脂多糖（LPS）处理的创伤不仅愈合延迟，而且创伤组织中促炎细胞因子如肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1 β（IL-1 β）和炎症介质蛋白高迁移率族蛋白1（HMGB-1）的表达水平显著升高。然而，用EO（lav）治疗LPS诱导的慢性伤口加速伤口愈合并降低IL-1 β和HMGB-1表达水平。进一步发现LPS诱导巨噬细胞焦亡产生IL-1 β。经EO（lav）处理后，巨噬细胞焦亡标志物Gasdermin D（GSDMD）的表达水平和焦亡相关的细胞毒性效应显著降低。免疫荧光结果也直接表明，EO（lav）可以保护巨噬细胞免受LPS诱导的焦亡。此外，EO（lav）可下调caspase-11相关的焦萎信号通路中IL-1 β、GSDMD和核苷酸结合寡聚化结构域样受体蛋白3（NLRP 3）的表达水平。本研究表明，EO（lav）可以通过抑制巨噬细胞焦亡来减少促炎因子的产生并改善炎症反应，从而加速LPS诱导的慢性伤口愈合。
Chronic wounds seriously affect the quality of life of the elderly, obese people, and diabetic patients. The excessive inflammatory response is a key driver of delayed chronic wound healing. Although lavender essential oil (EO [lav]) has been proven to have anti-inflammatory and accelerate wound curative effects, the specific molecular mechanism involved is still ambiguous. The results showed that the wounds treated with lipopolysaccharide (LPS) not only had delayed healing, but also the expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and the inflammatory mediator protein, high-mobility group box 1 protein (HMGB-1), in the wound tissues were significantly increased. However, treatment of LPS-induced chronic wounds with EO (lav) accelerated wound healing and decreased IL-1 beta and HMGB-1 expression levels. It was further found that LPS induced macrophage pyroptosis to produce IL-1 beta. After treatment with EO (lav), the expression level of macrophage pyroptosis marker Gasdermin D (GSDMD) and pyroptosis-related cytotoxic effects were significantly reduced. Immunofluorescence results also directly indicate that EO (lav) can protect macrophages from LPS-induced pyroptosis. Moreover, EO (lav) can down-regulate expression levels of IL-1 beta, GSDMD, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the caspase-11-related pyroptotic signaling pathway. This study demonstrates that EO (lav) can reduce proinflammatory factor production and ameliorate inflammatory response by inhibiting macrophage pyroptosis, which accelerates LPS-induced chronic wound healing.