Pathogenesis of silicosis: Current concepts and hypotheses

Davis, Gerald S.

doi:10.1007/bf02713638

Cited by 142 publications

(51 citation statements)

References 35 publications

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“…Macrophages play an important role in the pathogenesis of silica-induced lung fibrosis in part through their ability to clear silica particles and apoptotic cells from the lung (1,49). In addition, macrophages are the initial source of inflammatory mediators produced in response to silica exposure that include oxygen radicals, leukotrienes, cytokines, and growth factors (1).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Tumor Necrosis Factor Receptor 1 (p55) Protects Macrophages from Silica-induced Apoptosis

Gambelli

Niu³

et al. 2004

Journal of Biological Chemistry

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Macrophages play a fundamental role in silicosis in part by removing silica particles and producing inflammatory mediators in response to silica. Tumor necrosis factor ␣ (TNF␣) is a prominent mediator in silicosis. Silica induction of apoptosis in macrophages might be mediated by TNF␣. However, TNF␣ also activates signal transduction pathways (NF-B and AP-1) that rescue cells from apoptosis. Therefore, we studied the TNF␣-mediated mechanisms that confer macrophage protection against the pro-apoptotic effects of silica. We will show that exposure to silica induced TNF␣ production by RAW 264.7 cells, but not by IC-21. Silica-induced activation of NF-B and AP-1 was only observed in RAW 264.7 macrophages. ERK activation in response to silica exposure was only observed in RAW 264.7 macrophages, whereas activation of p38 phosphorylation was predominantly observed in IC-21 macrophages. No changes in JNK activity were observed in either cell line in response to silica exposure. Silica induced apoptosis in both macrophage cell lines, but the induction of apoptosis was significantly larger in IC-21 cells. Protection against apoptosis in RAW 264.7 cells in response to silica was mediated by enhanced NF-B activation and ERKmediated phosphorylation of the p55 TNF␣ receptor. Inhibition of these two protective mechanisms by specific pharmacological inhibitors or transfection of dominant negative mutants that inhibit IB␣ or ERK phosphorylation significantly increased silica-induced apoptosis in RAW 264.7 macrophages. These data suggest that NF-B activation and ERK-mediated phosphorylation of the p55 TNF receptor are important cell survival mechanisms in the macrophage response to silica exposure.

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Section: Discussionmentioning

confidence: 99%

Phosphorylation of Tumor Necrosis Factor Receptor 1 (p55) Protects Macrophages from Silica-induced Apoptosis

Gambelli

Niu³

et al. 2004

Journal of Biological Chemistry

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“…Inhalation of inorganic minerals and coal mine dust can produce pneumoconiosis, a lung disease characterized by an initial pulmonary inflammatory response in the lung associated with an increase in cell-mediated secretions of cytokines, growth factors, lysosomal enzymes, hydrogen peroxide, and superoxide anion (1)(2)(3)(4). Several studies suggest that many of these factors work together to cause cell injury and the progression of the disease process (3,4).…”

Section: Introductionmentioning

confidence: 99%

Generation of Oxygen Radicals by Minerals and Its Correlation to Cytotoxicity

Vallyathan¹

1994

Environmental Health Perspectives

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Occupational exposure to mineral dust causes pneumoconiosis and other diseases. A cytotoxicity assay to predict the potential of minerals to cause disease would be of great value as a prevention strategy. This study compares the ability of several minerals to generate the more potent oxidizing agent, hydroxyl radical (OH), and their cytotoxicity and lipid peroxidation potentials. Crystalline silica, the most potent cytotoxic and pathogenic mineral studied, showed the least ability to generate *OH radicals while inducing the maximal lipid peroxidation. Coal mine dust, showing the maximal ability to generate *OH radicals, was the least cytotoxic in bioassays of toxicity and induction of lipid peroxidation. Based on these results, it would appear that the ability of minerals to induce lipid peroxidation provides a better correlation with known cytotoxicity and pathogenicity of minerals than does their ability to generate oxygen radicals. -Environ Health Perspect 102(Suppl 10):1 1 1-1 15 (1994)

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“…he inhalation sult to silicopro sequently, chro [24] [21] , w onic bronchitis elop due to the is typified by f take restriction spiratory tract to phagasomes active oxygen ncreased protr epithelial cell the production equently releas inflammations ion region. The agen fibers on t the upper lu e opacities and iomedical Engin for well improv [12] .…”

Section: Rcs Expomentioning

confidence: 99%

Modelling the health risks of exposure to respirable crystalline silica from hydraulic fracturing operations in the USA shale plays

Olawoyin

2015

JBEI

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Respirable crystalline silica (RCS) is a known human carcinogen and a contaminant of potential concern. Proppants are used during the process of well stimulation (hydraulic fracturing) as additives in the fluid cocktail and sand is often used as a proppant which contains high percentage of silica determined by the quartz content. Empirical occupational exposure risk models were employed in this study to assess the potential health consequences from chronic RCS exposures based on RCS data from NIOSH and risk assessment formulas. Evaluating the lifetime (LT) excess cancer risk (LCR) potential, based on a risk target of 10 5 , the job titles that are likely to experience any substantial potential effect of cancer induction are the sand mover (LCR = 16.1 × 10 5 ) and transfer belt (LCR = 19.2 × 10 5 ) operators. The sand truck driver and data Van operators are among the job functions with a cumulative disease burden of 7.2% that are unlikely to be affected by < 2% carcinogenic disease burden. The chemical truck, sand mover and transfer belt (T-belt) operators may potentially be at risk of other occupational nonmalignant respiratory diseases with hazard quotient (HQ) of 0.65, 1.79, and 2.13 respectively. It is recommended that continuous occupational health monitoring of potentially exposed workers should be included as part of the project plan and the engineering risk controls that have been put in place should be ranked to highlight the effectiveness of any risk reduction/prevention methodology employed.

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Pathogenesis of silicosis: Current concepts and hypotheses

Cited by 142 publications

References 35 publications

Phosphorylation of Tumor Necrosis Factor Receptor 1 (p55) Protects Macrophages from Silica-induced Apoptosis

Phosphorylation of Tumor Necrosis Factor Receptor 1 (p55) Protects Macrophages from Silica-induced Apoptosis

Generation of Oxygen Radicals by Minerals and Its Correlation to Cytotoxicity

Modelling the health risks of exposure to respirable crystalline silica from hydraulic fracturing operations in the USA shale plays

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