研究动态
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以单细胞分辨率分析皮下角叉菜胶小鼠模型中拉伸对炎症的影响。

Effect of stretching on inflammation in a subcutaneous carrageenan mouse model analyzed at single-cell resolution.

发表日期:2023 Nov 01
作者: Lisbeth Berrueta, Dennis Muñoz-Vergara, Daniel Martin, Rebecca Thompson, Brian E Sansbury, Matthew Spite, Gary J Badger, Helene M Langevin
来源: JOURNAL OF CELLULAR PHYSIOLOGY

摘要:

了解影响炎症生物反应的因素至关重要,因为它参与生理和病理过程,包括组织修复/愈合、癌症、感染和自身免疫性疾病。我们之前已经证明,体内拉伸可以减少大鼠炎症并增加局部促消退脂质介质,这表明对炎症消退有直接的机械作用。在这里,我们的目的是进一步探讨拉伸在小鼠皮下角叉菜胶炎症模型中在细胞/分子水平上的影响。每天两次拉伸 10 分钟可减少炎症,在注射角叉菜胶后 48 小时增加促消解介质途径中间体 17-HDHA 的产生,并在注射 96 小时时减少促消解介质和促炎介质(例如 PGE2 和 PGD2) 。 96 小时时炎症病变的单细胞 RNA 测序分析表明,拉伸增加了 96 小时时 M1 和 M2 巨噬细胞中促炎 (Nos2) 和促消退 (Arg1) 基因的表达。细胞间通讯分析预测了中性粒细胞和 M2a 巨噬细胞协调的特定配体-受体相互作用,表明中性粒细胞的持续存在会招募免疫细胞(例如活化的巨噬细胞)来容纳抗原,同时促进分辨率和保持组织稳态。© 2023 Wiley periodicals LLC。
Understanding the factors that influence the biological response to inflammation is crucial, due to its involvement in physiological and pathological processes, including tissue repair/healing, cancer, infections, and autoimmune diseases. We have previously demonstrated that in vivo stretching can reduce inflammation and increase local pro-resolving lipid mediators in rats, suggesting a direct mechanical effect on inflammation resolution. Here we aimed to explore further the effects of stretching at the cellular/molecular level in a mouse subcutaneous carrageenan-inflammation model. Stretching for 10 min twice a day reduced inflammation, increased the production of pro-resolving mediator pathway intermediate 17-HDHA at 48 h postcarrageenan injection, and decreased both pro-resolving and pro-inflammatory mediators (e.g., PGE2 and PGD2 ) at 96 h. Single-cell RNA sequencing analysis of inflammatory lesions at 96 h showed that stretching increased the expression of both pro-inflammatory (Nos2) and pro-resolution (Arg1) genes in M1 and M2 macrophages at 96 h. An intercellular communication analysis predicted specific ligand-receptor interactions orchestrated by neutrophils and M2a macrophages, suggesting a continuous neutrophil presence recruiting immune cells such as activated macrophages to contain the antigen while promoting resolution and preserving tissue homeostasis.© 2023 Wiley Periodicals LLC.