Exercise training inhibits macrophage-derived IL-17A-CXCL5-CXCR2 inflammatory axis to attenuate pulmonary fibrosis in mice exposed to silica

Fuyu Jin; Yaqian Li; Xuemin Gao; Xinyu Yang; Tian Li; Shupeng Liu; Zhongqiu Wei; Shifeng Li; Na Mao; Heliang Liu; Wenchen Cai; Hong Xu; Haibo Zhang

doi:10.1016/j.scitotenv.2023.166443

Exercise training inhibits macrophage-derived IL-17A-CXCL5-CXCR2 inflammatory axis to attenuate pulmonary fibrosis in mice exposed to silica

Sci Total Environ. 2023 Dec 1:902:166443. doi: 10.1016/j.scitotenv.2023.166443. Epub 2023 Aug 21.

Authors

Fuyu Jin¹, Yaqian Li¹, Xuemin Gao¹, Xinyu Yang¹, Tian Li¹, Shupeng Liu¹, Zhongqiu Wei¹, Shifeng Li¹, Na Mao¹, Heliang Liu², Wenchen Cai³, Hong Xu⁴, Haibo Zhang⁵

Affiliations

¹ School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China.
² School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address: liuheliang@ncst.edu.cn.
³ School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address: caiwenchen@ncst.edu.cn.
⁴ School of Public Health, Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology, Tangshan, Hebei 063210, China; Health Science Center, North China University of Science and Technology, Tangshan, Hebei 063210, China. Electronic address: xuhong@ncst.edu.cn.
⁵ Department of Anesthesiology and Pain Medicine, Department of Physiology, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; The Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada.

PMID: 37611700
DOI: 10.1016/j.scitotenv.2023.166443

Abstract

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.

Keywords: CXC motif chemokine; Inflammatory response; Interleukin-17A; Silicosis.

MeSH terms

Animals
Chemokine CXCL5 / metabolism
Chemokines / metabolism
Exercise* / physiology
Inflammation
Interleukin-17 / metabolism
Macrophages / metabolism
Mice
Mice, Inbred C57BL
Pulmonary Fibrosis* / chemically induced
Pulmonary Fibrosis* / metabolism
Pulmonary Fibrosis* / therapy
Receptors, Interleukin-8B / metabolism
Silicon Dioxide / toxicity
Silicosis* / metabolism
Silicosis* / therapy

Substances

Chemokines
Interleukin-17
Silicon Dioxide
Chemokine CXCL5
Receptors, Interleukin-8B