Gypsum alleviates pneumonia via the gut–lung axis by mediating ILC2 compartmental migration

Ziming Zhuang , Huiqing Zhu , Jing Xu , Lizhen Lin , Feilong Chen , Cuiping Jiang , Qingfa Tang
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Abstract

Introduction

Bacterial pneumonia is a common lower respiratory tract infectious disease. Gypsum, a type of calcium sulfate mineral, primarily consists of calcium sulfate and contains trace amounts of other metallic elements. In traditional Chinese medicine, gypsum has been widely applied, possessing effects such as heat-clearing, detoxification, cooling blood, arresting bleeding, reducing swelling, and alleviating pain. The purpose of this study was to investigate the mechanism of gypsum inhibition of Streptococcus pneumoniae -induced pneumonia by mediating interregional migration of ILC2 through the gut-lung axis.

Methods

Normal pneumonia model was induced by Streptococcus pneumoniae, and pseudo-sterile mouse model was established using broad-spectrum antibiotics. The influence of gypsum on the intestinal flora was analyzed using 16S rDNA. Flow cytometry was used to analyze the typing and content of ILC2 in mouse mesenteric lymph nodes and lung tissues. The expression levels of inflammatory cytokines and specific targets associated with immune migration were assessed using ELISA, RT-qPCR, and western blotting methods. And the effects of gypsum on mucosal barrier using IHC.

Results

Gypsum effectively alleviates pulmonary inflammation in mice with pneumonia. Gypsum restores the gut microbiota in mice with Streptococcus pneumoniae and gypsum can regulate the expression of miR-155, miR-146a, IL-25, and S1P, promoting the migration of intestinal ILC2s to the lungs. Finally promotes type 2 immunity, alleviating pneumonia and restore lung mucosal barrier.

Discussion

Our study contributes to the understanding of gypsum's function in treating infectious pulmonary conditions. Its mechanism involves remedying gut dysbiosis and initiating ILC2 migration, culminating in decreased lung inflammation and enhanced mucosal immunity in the lungs.

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石膏通过肠肺轴介导 ILC2 区间迁移缓解肺炎
导言细菌性肺炎是一种常见的下呼吸道传染病。石膏是一种硫酸钙矿物,主要成分是硫酸钙,并含有微量的其他金属元素。石膏具有清热、解毒、凉血、止血、消肿、止痛等功效,在中药中应用广泛。方法用肺炎链球菌诱导正常肺炎模型,使用广谱抗生素建立假性无菌小鼠模型。使用 16S rDNA 分析石膏对肠道菌群的影响。流式细胞术分析了小鼠肠系膜淋巴结和肺组织中 ILC2 的分型和含量。使用 ELISA、RT-qPCR 和 Western 印迹法评估了炎性细胞因子和与免疫迁移相关的特定靶点的表达水平。结果 石膏能有效缓解肺炎小鼠的肺部炎症。石膏能恢复肺炎链球菌小鼠的肠道微生物群,并能调节 miR-155、miR-146a、IL-25 和 S1P 的表达,促进肠道 ILC2 向肺部迁移。我们的研究有助于理解石膏在治疗肺部感染性疾病方面的功能。其机制包括纠正肠道菌群失调和启动 ILC2 迁移,最终减少肺部炎症和增强肺部粘膜免疫。
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