establishing-silicosis-rat-model-via-exposure-whole-body-to

Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica

The major cause of silicosis is the inhalation of silica in the occupational environment. Despite some anatomical and physiological differences, rodent ...

North China University of Science and Technology

Silicosis is the most prevalent occupational disease in China. It is a form of pulmonary fibrosis caused by the inhalation of silicon particles. As there is no cure for the potentially lethal and progressive condition, the treatment of silicotic fibrosis is an important and difficult problem to address. Thalidomide, a drug with anti-inflammatory and immunoregulatory properties, has been reported to have lung-protective effects. The purpose of this study was to observe the therapeutic effect of thalidomide on silicotic mice and to determine the protective mechanism. By using silicotic mice models and MH-S cells, we found the expression of endoplasmic reticulum stress (ER stress) and Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) pathway as well as inflammation-related factors were upregulated in the macrophages of silicotic mice. The same indexes were detected in silica-stimulated MH-S cells, and the results were consistent with those in vivo. That is, silica activated ER stress and the TLR4-NF-κB pathway as well as the inflammatory response in vitro. Treating both silicotic mice and silica-stimulated MH-S cells with thalidomide inhibited ER stress and the TLR4-NF-κB pathway as well as the inflammatory response. The present study demonstrates thalidomide as a potential therapeutic agent against silicosis.

Thalidomide Alleviates Pulmonary Fibrosis Induced by Silica in Mice by Inhibiting ER Stress and the TLR4-NF-κB Pathway.

Mechanisms of silicosis have yet to be clarified, and pathological conditions are inaccurately described in some experimental studies on silicosis. This study was aimed at describing initial lesions in silicosis, as observed in rats with silica exposure via inhalation, and major histopathologic alterations. Male Wistar rats were exposed to silica for 24 weeks. Hematoxylin and eosin staining indicated the presence of "cellular nodule+ macrophage alveolitis" in rats exposed to silica from the 2-16 weeks time points and "fibrotic cellular + cellular nodule" in rats exposed to silica via inhalation for 24 weeks. By immunohistochemistry, the following were noted: a continual increase in the positive expression of CD68 in macrophages in the lungs of rats exposed to silica; hyperplasia in alveolar type II cells (AT2); loss of original phenotypes in fibrotic cellular nodules, macrophages, and AT2 cells; loss of endothelial cells in silicotic nodules; and positive expression of α-smooth muscle actin in macrophages. Typical pathological changes in silicosis were also summarized. Among these changes were macrophage alveolitis, cellular nodules, and fibrotic cellular nodules, including an increase in minute cellular nodules in the early stages and the formation of fibrotic cellular nodules in the late stages.

Minute Cellular Nodules as Early Lesions in Rats with Silica Exposure via Inhalation.

Quercetin exerts anti-inflammatory, anti-oxidant and other protective effects. Previous studies have shown that senescent cells, such as fibroblasts and type II airway epithelial cells, are strongly implicated in the development of pulmonary fibrosis pathology. However, the role of senescent macrophages during silicosis remains unclear. We investigated the effects of quercetin on macrophage senescence and pulmonary fibrosis, and explored underlying mechanisms. Mice were randomized to six model groups. Vitro model was also established by culturing RAW264.7 macrophages with silica (SiO). We examined the effects of quercetin on fibrosis, senescence-associated β-galactosidase (SA-β-Gal) activity, and senescence-specific genes (p16, p21, and p53). We showed that quercetin reduced pulmonary fibrosis and inhibited extracellular matrix (ECM) formation. Quercetin also attenuated macrophage senescence induced by SiO both  and . In addition, quercetin significantly decreased the expressions of the senescence-associated secretory phenotype (SASP), including proinflammatory factors (interleukin-1α (Il-1α), Il-6, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1)) and matrix metalloproteinases (MMP2, MMP9, and MMP12). In conclusion, quercetin mediated its anti-fibrotic effects by inhibiting macrophage senescence, possibly via SASP.

Tian Li

Hebei Key Laboratory for Organ Fibrosis Research,
School of Public Health,
Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health

North China University of Science and Technology

Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica

Tian Li

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Hebei Key Laboratory for Organ Fibrosis Research,School of Public Health,Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health

North China University of Science and Technology

Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica

Hebei Key Laboratory for Organ Fibrosis Research,
School of Public Health,
Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health