title: Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice.
abstract: Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4+ T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice.
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China; Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Laiyu
authors.initials: L
authors.lastname: Song
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Wujing
authors.initials: W
authors.lastname: Dai
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Lu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, Liaoning, PR China. Electronic address: chenjie@mail.cmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control*; D011897:Random Allocation; D012829:Silicosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D057134:Antibodies, Neutralizing; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C587672:IL1B protein, mouse; C098680:Il17a protein, mouse; C577686:interleukin-6, mouse
keywords: IL-17A; Lung Inflammation; Lung fibrosis; Silica; Th17