EMAIL THIS PAGE TO A FRIEND

Journal of cellular and molecular medicine

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


PMID 25091058

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.