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.

The acute airway inflammation induced by PM2.5 exposure and the treatment of essential oils in Balb/c mice

“…IL-1β production from effected cells has been found in many kinds of lung inflammatory reactions induced by viruses, bacteria and drugs1314. Some in vitro studies found that PM 2.5 could induce the secretion of IL-1β from macrophags through multiple pathways15.…”

Bronchoalveolar Lavage Fluid microRNA-146a

“…Altered expression levels of interleukins and tumor necrosis factora in response to inflammation have been observed in silicosis. [31][32][33] Baltimore et al 34 illustrated that the expression levels of interleukin-1 receptor-associated kinase 1 and tumor necrosis factor receptorassociated factor 6 were down regulated by administering a miR-146 oligonucleotide in target cells. Therefore, miR-146a may be involved in silicosis and pulmonary function through a variety of inflammatory cytokines, forming a complex regulatory network.…”

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

“…IL‐1β is a protein known by its crucial pathophysiological role in inflammatory disorders and its influence in silicosis susceptibility and/or severity has been investigated in several animal model studies, and in a clinical study . We hypothesized that there is a possible association of the IL1B +3954C>T polymorphism with the severity of silicosis, since this polymorphism has been previously associated with the severity and susceptibility to several inflammatory diseases .…”

“…Interleukin 1 beta (IL‐1β), Interleukin 1 alpha (IL‐1α), and tumor necrosis factor‐alpha (TNF‐α) are proinflammatory cytokines associated with the physiopathology of both silicosis and Tb . They are encoded by polymorphic genes with a range of SNPs described, which can influence the activity or expression level of the codified proteins.…”