Connective Tissue Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland, USA.
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Cell Physiol. 2023 Dec;238(12):2778-2793. doi: 10.1002/jcp.31133. Epub 2023 Nov 1.
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., PGE and PGD ) 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.
了解影响炎症生物反应的因素至关重要，因为炎症参与了生理和病理过程，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，体内拉伸可以减少炎症并增加大鼠体内局部的促解决脂质介质，表明其对炎症消退有直接的机械作用。在这里，我们旨在进一步探索在小鼠皮下角叉菜胶炎症模型中，拉伸在细胞/分子水平上的作用。每天拉伸两次，每次 10 分钟，可减轻炎症，在角叉菜胶注射后 48 小时增加促解决介质途径中间产物 17-HDHA 的产生，并在 96 小时降低促解决和促炎介质（例如 PGE 和 PGD）的水平。96 小时时炎症病变的单细胞 RNA 测序分析表明，拉伸增加了 M1 和 M2 巨噬细胞中促炎（Nos2）和促解决（Arg1）基因的表达。细胞间通讯分析预测了由中性粒细胞和 M2a 巨噬细胞协调的特定配体-受体相互作用，表明持续存在的中性粒细胞招募免疫细胞（如激活的巨噬细胞）来控制抗原，同时促进解决并维持组织内稳态。
