title: Th17 can regulate silica-induced lung inflammation through an IL-1β-dependent mechanism.
abstract: Silicosis is an occupational lung disease caused by the inhalation of silica dust and characterized by lung inflammation and fibrosis. Interleukin (IL)-1β is induced by silica and functions as the key pro-inflammatory cytokine in this process. The Th17 response, which is induced by IL-1β, has been reported very important in chronic human lung inflammatory diseases. To elucidate the underlying mechanisms of IL-1β and IL-17 in silicosis, we used anakinra and an anti-IL-17 monoclonal antibody (mAb) to block the receptor of IL-1β (IL-RI) and IL-17, respectively, in a mouse model of silicosis. We observed increased IL-1β expression and an enhanced Th17 response after silica instillation. Treatment with an IL-1 type I receptor (IL-1RI) antagonist anakinra substantially decreased silica-induced lung inflammation and the Th17 response. Lung inflammation and the accumulation of inflammatory cells were attenuated in the IL-17-neutralized silicosis group. IL-17 may promote lung inflammation by modulating the differentiation of Th1 and regulatory T cells (Tregs) and by regulating the production of IL-22 and IL-1β during the lung inflammation of silicosis. Silica may induce IL-1β production from alveolar macrophages and promote inflammation by initiating a Th17 response via an IL-1β/IL-1RI-dependent mechanism. The Th17 response could induce lung inflammation during the pathogenesis of silicosis by regulating the homoeostasis of the Th immune responses and affecting the production of IL-22 and IL-1β. This study describes a potentially important inflammatory mechanism of silicosis that may bring about novel therapies for this inflammatory and fibrotic disease.
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China; Department of Clinical Immunology, Dalian Medical University, Dalian, China.
authors.forename: Laiyu
authors.initials: L
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.forename: Wujing
authors.initials: W
authors.lastname: Dai
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Fangwei
authors.initials: F
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology*; D007378:Interleukins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D012822:Silicon Dioxide; D012829:Silicosis / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D007378:Interleukins; D053573:Receptors, Interleukin-1 Type I; D012822:Silicon Dioxide; D000097043:Interleukin-22; C587672:IL1B protein, mouse; C583355:IL1R1 protein, mouse
keywords: IL-1β; Th17; lung Inflammation; silicosis
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