School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China.
School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China.
Sci Total Environ. 2023 Dec 1;902:166443. doi: 10.1016/j.scitotenv.2023.166443. Epub 2023 Aug 21.
Exposure to crystalline silica leads to health effects beyond occupational silicosis. Exercise training's potential benefits on pulmonary diseases yield inconsistent outcomes. In this study, we utilized experimental silicotic mice subjected to exercise training and pharmacological interventions, including interleukin-17A (IL-17A) neutralizing antibody or clodronate liposome for macrophage depletion. Findings reveal exercise training's ability to mitigate silicosis progression in mice by suppressing scavenger receptor B (SRB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Toll-like receptor 4 (TLR4) pathways. Macrophage-derived IL-17A emerges as primary source and trigger for silica-induced pulmonary inflammation and fibrosis. Exercise training effectively inhibits IL-17A-CXC motif chemokine ligand 5 (CXCL5)-Chemokine (C-X-C motif) Receptor 2 (CXCR2) axis in silicotic mice. Our study evidences exercise training's potential to reduce collagen deposition, preserve elastic fibers, slow pulmonary fibrosis advancement, and enhance pulmonary function post silica exposure by impeding macrophage-derived IL-17A-CXCL5-CXCR2 axis.
暴露于结晶二氧化硅会导致除职业性矽肺以外的健康影响。运动训练对肺部疾病的潜在益处产生了不一致的结果。在这项研究中，我们利用实验性矽肺小鼠进行运动训练和药物干预，包括白细胞介素-17A（IL-17A）中和抗体或氯膦酸盐脂质体以耗尽巨噬细胞。研究结果表明，运动训练通过抑制清道夫受体 B（SRB）/NOD 样受体热蛋白结构域相关蛋白 3（NLRP3）和 Toll 样受体 4（TLR4）途径，能够减轻小鼠矽肺的进展。巨噬细胞来源的 IL-17A 是二氧化硅诱导的肺部炎症和纤维化的主要来源和触发因素。运动训练可有效抑制矽肺小鼠中 IL-17A-CXC 基序趋化因子配体 5（CXCL5）-趋化因子（C-X-C 基序）受体 2（CXCR2）轴。我们的研究证明了运动训练通过阻止巨噬细胞来源的 IL-17A-CXCL5-CXCR2 轴，减少胶原沉积、保留弹性纤维、减缓矽肺后肺纤维化进展和增强肺功能的潜力。
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