Abstract
Silicosis is one of the most common occupational respiratory diseases caused by inhaling silica dust over a prolonged period of time, and the progression of silicosis is accompanied with chronic inflammation and progressive pulmonary fibrosis, in which dendritic cells (DCs), the most powerful antigen presentation cell (APC) in the immune response, play a crucial role. To investigate the role of DCs in the development of silicosis, we established an experimental silicosis rat model and examined the number of DCs and alveolar macrophages (AMs) in lung tissues using immunofluorescence over 84 days. Additionally, to obtain an overview of the immunological changes in rat lung tissues, a series of indicators including Th1/Th2 cells, IFN-γ, IL-4, MHC-II, CD80/86 and IL-12 were detected using flow cytometry and an enzyme-linked immunosorbent assay (ELISA) as well as a real-time polymerase chain reaction (PCR) assay. We observed that the number of DCs slightly increased at the inflammatory stage, and it increased significantly at the final stage of fibrosis. Polarization of Th1 cells and IFN-γ expressions were dominant during the inflammatory stage, whereas polarization of Th2 cells and IL-4 expressions were dominant during the fibrotic stage. The subsequent mechanistic study found that the expressions of MHC-II, CD80/86 and IL-12, which are the key molecules that connect DCs and Th cells, changed dynamically in the experimental silicosis rat model. The data obtained in this study indicated that the increase in DCs may contribute to polarization of Th1/Th2 cells via MHC-II, CD80/86, and IL-12 in silica dust-exposed rats.
Highlights
Silica dust is one of the most common environmental and occupational risk factors; long term exposure to silica dust contributes to the development of a number of diseases including silicosis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).[1]
The difference in alveolar macrophages (AMs) numbers between silica dust exposure rats and control was statistically signi cant at each time point except for the results of the 21st day (P < 0.05); the number of dendritic cells (DCs) increased from the 1st day, and even more DCs were observed on the 42th day in the silica dust exposure rats
We detected the number of AMs and DCs in rat lung tissue over 84 days by ow cytometry
Summary
Silica dust is one of the most common environmental and occupational risk factors; long term exposure to silica dust contributes to the development of a number of diseases including silicosis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).[1]. The Si–OH complex of silica and H2O is similar to pathogen-associated molecular patterns (PAMPs) and it is recognized and bound by pattern recognition receptors (PRRs) on AMs;[11] it can induce AMs to secret cytokines and chemokines to initiate the in ux of in ammatory cells such as macrophages, neutrophils, and lymphocytes.[12,13] Upon activation of the innate immune system, silicosis presents an acute in ammatory reaction at an early stage, which is characterized by in ltration of in ammatory cells and destruction of alveolar walls. Accompanied by the activation of in ammatory cells and the secretion of cytokines and chemokines, adaptive immunity is involved in the development of silicosis. Many broblasts are activated and proliferated, releasing a large amount of collagen; silicosis progresses to diffuse interstitial brosis or eventually form silicotic nodules.[14,15] Previous studies have demonstrated that 26108 | RSC Adv., 2018, 8, 26108–26115
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