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Th17 can regulate silica-induced lung inflammation through an IL-1?-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)-1? is induced by silica and functions as the key pro-inflammatory cytokine in this process. The Th17 response, which is induced by IL-1?, has been reported very important in chronic human lung inflammatory diseases. To elucidate the underlying mechanisms of IL-1? and IL-17 in silicosis, we used anakinra and an anti-IL-17 monoclonal antibody (mAb) to block the receptor of IL-1? (IL-RI) and IL-17, respectively, in a mouse model of silicosis. We observed increased IL-1? 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-1? during the lung inflammation of silicosis. Silica may induce IL-1? production from alveolar macrophages and promote inflammation by initiating a Th17 response via an IL-1?/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-1?. This study describes a potentially important inflammatory mechanism of silicosis that may bring about novel therapies for this inflammatory and fibrotic disease.

SUBMITTER: Song L

PROVIDER: S-EPMC4196653 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Th17 can regulate silica-induced lung inflammation through an IL-1β-dependent mechanism.

Song Laiyu L Weng Dong D Dai Wujing W Tang Wen W Chen Shi S Li Chao C Chen Ying Y Liu Fangwei F Chen Jie J

Journal of cellular and molecular medicine 20140805 9

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) ...[more]

PMID: 25091058

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Project description:Interleukin-1β (IL-1β) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1β-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1β activity by blocking IL-1β-IL-1R1 interaction in OA. In this study, we report the anti-IL-1β activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1β-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1β-IL-1R1 interaction by direct binding to IL-1β using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1β bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1β-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1β-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1β-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1β-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1β-related diseases by hindering IL-1β-IL-1R1 interaction and suppressing IL-1β bioactivity.

Dataset Information

Th17 can regulate silica-induced lung inflammation through an IL-1?-dependent mechanism.

Publications

Th17 can regulate silica-induced lung inflammation through an IL-1β-dependent mechanism.

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