The Sources of Inflammatory Mediators in the Lung after Silica Exposure

Rao, K. Murali Krishna; Porter, Dale W.; Meighan, Terence; Castranova, Vince

doi:10.1289/ehp.7295

Cited by 62 publications

(44 citation statements)

References 67 publications

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“…20,21 A study examining the effect of silica exposure on the production of inflammatory mediators in the lung has shown upregulation of IL-6 and MCP-1 in alveolar macrophages and fibroblasts. 22 Therefore, in the present study the increased levels of Ccl2 and IL-6 mRNA expression in the lungs of CB-treated rats may account for the differences in the circulating levels of IL-6 and MCP-1 between the 2 groups. Cytokines associated with inflammation are known to trigger the production of acute-phase proteins, with IL-6 being the major stimulator of CRP synthesis in the liver.…”

Section: Discussionmentioning

confidence: 57%

Inhalation Exposure to Carbon Black Induces Inflammatory Response in Rats

Niwa¹,

Hiura²,

Sawamura³

et al. 2008

Circ J

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xposure to particulate matter air pollution has been reported to be associated with death and hospitalization from cardiovascular causes. 1,2 The mechanism by which long-term exposure to fine particulate matter increases the risk of cardiovascular disease remains uncertain. Accelerated atherosclerosis and vulnerability to plaque rupture have been documented in experimental animal models exposed to particulate matter, 3,4 and ambient pollution has been correlated with elevated blood pressure (BP) 5-8 and heart rate (HR) 9 in humans. Moreover, the duration of exhaust exposure in highway toll collectors has been shown to be associated with carotid intima -media thickening. 10 We recently showed that a 10-week intra-tracheal dispersion of carbon black (CB) induced atherosclerosis in low-density lipoprotein receptor knock-out (LDLR/KO) mice and the explanation appeared to be the inflammatory responses against deposited CB in the lungs. 11 It has been postulated that inhalation of fine particulate matter might cause inflammation in the lung, and that this low-grade and prolonged inflammation might accelerate atherothrombotic diseases. 12,13 On the other hand, a more direct role of nanomaterials has been proposed, based on the study by Nemmar et al that showed rapid translocation of inhaled nano-sized carbon particles into the bloodstream of humans. 14 Our in-vitro studies also suggested that nano-sized particulate matter might penetrate alveoli into circulating blood, and might directly damage endothelial cells, activate mononuclear cells, and aggregate platelets to accelerate the formation of atherothrombotic diseases. [15][16][17] In our previous analysis of the effect of CB exposure in LDLR/KO mice, 11 CB was not detected in tissues other than the lungs. Thus, it is unlikely that dispersed CB translocates into the circulating blood and directly damages target tissues or cells. However, the method of CB exposure in the previous study was intratracheal dispersion, which might not mimic the physiological responses elicited by the common route of exposure in humans. It is possible that CB particles administered by intra-tracheal dispersion may more easily aggregate and deposit in alveolar regions than CB particles dispersed in the respiratory air. With whole-body inhalation exposure to nano-sized CB particles, CB might translocate into circulating blood and reach target tissues. To assess this possibility, we examined whether exposure of rats to nano-sized CB particles by inhalation causes translocation of CB particles into the circulation and increases cardiovascular risk by exerting direct adverse effects on extrapulmonary tissues. Inhalation Exposure to Carbon Black Induces Inflammatory Response in RatsYasuharu Niwa, PhD*; Yumiko Hiura, PhD*; Hiromi Sawamura, MS; Naoharu Iwai, MD Background A link between exposure to fine particulate matter and cardiovascular events has been established. Inhaled nanoparticles are thought to pass through the lungs to reach other tissues via systemic circulation and to induce cell or...

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Section: Discussionmentioning

confidence: 57%

Inhalation Exposure to Carbon Black Induces Inflammatory Response in Rats

Niwa¹,

Hiura²,

Sawamura³

et al. 2008

Circ J

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“…It is well accepted that the proinflammatory functions of IL-17 and -22 are due to their capacities to stimulate neutrophilic factors released by epithelial cells. KC and MIP-2, two IL-8-related cytokines and powerful neutrophil chemoattractants, are produced by alveolar epithelial cells after silica exposure (52,53), and neutralization experiments showed that both chemokines play an important role in the accumulation of lung neutrophils in silica-treated rats (54). The reduced production of KC and MIP-2 in the lungs of silica-treated IL-17R-deficient mice newly supports that, in addition to silica, IL-17A-producing T lymphocytes exacerbate proinflammatory functions of epithelial cells during silicosis.…”

Section: Discussionmentioning

confidence: 99%

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

Re¹,

Dumoutier

Couillin

et al. 2010

The Journal of Immunology

130

107

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IL-17–producing T lymphocytes play a crucial role in inflammation, but their possible implication in fibrosis remains to be explored. In this study, we examined the involvement of these cells in a mouse model of lung inflammation and fibrosis induced by silica particles. Upregulation of IL-17A was associated with the development of experimental silicosis, but this response was markedly reduced in athymic, γδ T cell-deficient or CD4+ T cell-depleted mice. In addition, γδ T lymphocytes and CD4+ T cells, but not macrophages, neutrophils, NK cells or CD8 T cells, purified from the lungs of silicotic mice markedly expressed IL-17A. Depletion of alveolar macrophages or neutralization of IL-23 reduced upregulation of IL-17A in the lung of silicotic mice. IL-17R–deficient animals (IL-17R−/−) or IL-17A Ab neutralization, but not IL-22−/− mice, developed reduced neutrophil influx and injury during the early lung response to silica. However, chronic inflammation, fibrosis, and TGF-β expression induced by silica were not attenuated in the absence of IL-17R or -22 or after IL-17A Ab blockade. In conclusion, a rapid lung recruitment of IL-17A–producing T cells, mediated by macrophage-derived IL-23, is associated with experimental silicosis in mice. Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica.

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“…In our study, divergence is thought to have been caused either by control of translation into proteins or control of protein disintegration. There are reports 14,15) on the divergence of expression for other genes caused by exposure to silica. Williams et al 14) found that the mRNA levels of TGF accelerated in epithelial cell lines exposed to silica while protein levels did not.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of EC‐SOD, Mn‐SOD and CuZn‐SOD in Rat Lung Exposed to Crystalline Silica

Kim

Morimoto²,

Ogami³

et al. 2007

Journal of Occupational Health

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SOD protein levels were also significantly lower than the control group at 90 and 180 d recovery. There was prominent EC-SOD immunostaining mainly in the plasma and alveolar macrophages and strong Mn-SOD staining in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following crystalline silica exposure. There was less CuZn-SOD staining in epithelial cells at terminal bronchioles in the crystalline silica-exposed group. These findings suggest that these SOD isozymes may be related to lung injury induced by crystalline silica. (J Occup Health 2007; 49: 242-248)

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The Sources of Inflammatory Mediators in the Lung after Silica Exposure

Cited by 62 publications

References 67 publications

Inhalation Exposure to Carbon Black Induces Inflammatory Response in Rats

Inhalation Exposure to Carbon Black Induces Inflammatory Response in Rats

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

Differential Expression of EC‐SOD, Mn‐SOD and CuZn‐SOD in Rat Lung Exposed to Crystalline Silica

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