含汞制剂通过抑制 ERK1/2 通路来减少小鼠和人类中性粒细胞胞外诱捕网的形成。
Mercury-containing preparations attenuate neutrophil extracellular trap formation in mice and humans through inhibiting the ERK1/2 pathway.
机构信息
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing, 100010, China.
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing, 100010, China.
出版信息
J Ethnopharmacol. 2024 Mar 1;321:117421. doi: 10.1016/j.jep.2023.117421. Epub 2023 Nov 17.
ETHNOPHARMACOLOGICAL RELEVANCE
Neutrophil extracellular trap (NET) formation plays a crucial role in wound healing disorders, including chronic skin ulcers and diabetic foot ulcers (DFUs). Over the years, traditional Chinese topical medications, such as Cinnabar (composed of HgS and soluble mercury salt) and hydrargyria oxydum rubrum (containing HgO and soluble mercury salt), have been utilized for treating these ailments. Nevertheless, the fundamental processes remain mostly ambiguous.
AIM OF THE STUDY
This study sought to investigate the potential effects of topical mercury-containing preparations on the process of NET formation.
MATERIALS AND METHODS
Neutrophils isolated from healthy individuals and mouse models of type 1 and type 2 diabetes were cultured with phorbol 12-myristate 13-acetate (PMA), both with and without the mercury-containing preparations (MCP). The formation of NETs was monitored using confocal and scanning electron microscopes. Immunofluorescence and fluorescent probes were employed to assess the levels of citrulline histone H (Cit-H) and intracellular reactive oxygen species (ROS), respectively. The impact of MCP extracts on cytokine expression, peptidylarginine deiminase 4 (PAD4), and myeloperoxidase (MPO) was measured through Luminex and ELISA assays. Phagocytosis of human neutrophils was analyzed using Flow Cytometry. Finally, the phosphorylation levels of ERK were detected by western blotting.
RESULTS
Treatment with MCP led to a reduction in PAD4, Cit-H, and MPO expressions in neutrophils, consequently inhibiting PMA-induced NET formation. MCP treatment also dampened ERK1/2 activation in neutrophils. Furthermore, MCP exhibited inhibitory effects on the secretion of the cytokine IL-8 and ROS production while enhancing neutrophil phagocytosis.
CONCLUSION
Our findings suggest that MCP can mitigate the release of NETs, likely by suppressing the ERK1/2 signaling pathway.
民族药理学相关性
中性粒细胞胞外诱捕网（NET）的形成在包括慢性皮肤溃疡和糖尿病足溃疡（DFU）在内的伤口愈合障碍中起着至关重要的作用。多年来，传统的中药外用药物，如朱砂（由 HgS 和可溶性汞盐组成）和氧化汞红（含有 HgO 和可溶性汞盐），一直被用于治疗这些疾病。然而，其基本作用机制仍大多不明确。
研究目的
本研究旨在探讨含汞的局部制剂对 NET 形成过程的潜在影响。
材料与方法
用佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）培养来自健康个体和 1 型和 2 型糖尿病小鼠模型的中性粒细胞，同时加入和不加入含汞制剂（MCP）。用共聚焦和扫描电子显微镜监测 NET 的形成。用免疫荧光和荧光探针分别评估瓜氨酸组蛋白 H（Cit-H）和细胞内活性氧（ROS）的水平。通过 Luminex 和 ELISA 测定 MCP 提取物对细胞因子表达、肽基精氨酸脱亚氨酶 4（PAD4）和髓过氧化物酶（MPO）的影响。用流式细胞术分析人中性粒细胞的吞噬作用。最后，用 Western blot 检测 ERK 的磷酸化水平。
结果
MCP 处理导致中性粒细胞中 PAD4、Cit-H 和 MPO 的表达减少，从而抑制 PMA 诱导的 NET 形成。MCP 处理还抑制了中性粒细胞中 ERK1/2 的激活。此外，MCP 对细胞因子 IL-8 的分泌和 ROS 的产生具有抑制作用，同时增强了中性粒细胞的吞噬作用。
结论
我们的研究结果表明，MCP 可以通过抑制 ERK1/2 信号通路来减轻 NET 的释放。
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