Background Silicosis is a systemic disease featured by diffuse fibrosis of lung tissues caused by chronic inhalation of occupational dust containing high-level free SiO2. This is also an occupational disease with the highest incidence and prevalence rates in China. However, the pathogenesis of silicosis is still unclear. In recent years, the cytokines related to macrophage synthesis and secretion have gained much attention owing to their significant role in the development of silicosis fibrosis. Exploring the role of cytokines related to pulmonary macrophages may be an important part to reveal the mechanism of silicosis fibrosis.
Objective This experiment is conducted to investigate the expressions and changes of interleukin-1β (IL-1β), interleukin-17 (IL-17), and connective tissue growth factor (CTGF) mRNA in pulmonary macrophages in rats developing silicosis fibrosis.
Methods A total of 60 Wistar rats were randomly divided into six groups with 10 rats in each group:one control group and five exposure groups (15, 30, 60, 90, and 120 d exposure groups). The rats in the exposure groups were injected of 1 mL silica dust suspension (100 mg·mL-1) for one time by pulmonary injection after anesthesia, and the observations lasted for 15, 30, 60, 90, and 120 d, respectively. The rats in the control group were perfused with normal saline of the same volume after anesthesia. Pulmonary macrophages were obtained by alveolar lavage after designed observation time ended. The lung tissues of each group were subject to HE and Masson staining, and determined for hydroxyproline (HYP) levels in liver tissues and expressions of IL-1β, IL-17, and CTGF mRNA in pulmonary macrophages.
Results According to the staining results, the alveolar structure was slightly damaged and the collagen fibers were slightly increased in the 15 d exposure group; the pulmonary fibrosis was gradually obvious with the extension of silica dust exposure time; the whole lung showed diffuse fibrosis in the 120 d exposure group. Compared with the control group, the HYP levels in lung tissues were increased with the prolongation of exposure time (P < 0.05), and showed a rising linear trend (P < 0.05). The relative expression levels of IL-1β mRNA in the control group and five (15, 30, 60, 90, and 120 d) exposure groups were 1.00±0.44, 1.22±0.65, 2.58±0.54, 3.93±0.78, 7.11±1.14, and 16.89±0.85, respectively; the relative expression levels of IL-17 mRNA were 1.00±0.36, 4.25±2.49, 7.00±2.95, 14.75±3.95, 37.28±2.51, and 50.27±5.66, respectively; the relative expression levels of CTGF mRNA were 1.00±0.48, 3.87±0.29, 4.97±1.20, 11.08±0.60, 15.50±2.71, and 23.64±4.11, respectively. Compared with the control group, the mRNA expressions of selected cytokines in other exposure groups were significantly different (P < 0.05) and showed a linear rising trend (P < 0.05), except the IL-1β mRNA expression in the 15 d exposure group.
Conclusion Silica dust could induce increased expressions of IL-1β, IL-17, and CTGF mRNA in pulmonary macrophages with the prolongation of exposure time, which might be one of the mechanisms of silicosis fibrosis.
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