Modulation of eicosanoid production by human alveolar macrophages exposed to silica in vitro.

Koren, Hillel S.; Joyce, Marianne; Devlin, Robert B.; Becker, Susanne; Driscoll, Kevin E.; Madden, Michael C.

doi:10.1289/ehp.929777

Cited by 17 publications

(6 citation statements)

References 21 publications

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“…Inflammatory cells, such as macrophages and neutrophils, that migrate into the alveolar space after silica instillation, are well known to produce CysLTs and LTB 4 [29,30,31]. In addition to these inflammatory cells, lung fibroblasts and type II alveolar epithelial cells also produce both CysLTs and LTB 4 [32,33].…”

Section: Discussionmentioning

confidence: 99%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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Background: Although cysteinyl leukotrienes (CysLTs) have been implicated in the etiology of acute inflammatory diseases, recent studies have suggested that they also directly stimulate fibroblasts. However, their precise role in the pathogenesis of pulmonary fibrosis is unclear. Methods: In this study, we evaluated the effect of both short- and long-term treatment with pranlukast, a CysLT type 1 (CysLT₁) receptor antagonist, on silica-induced pulmonary fibrosis in mice, which is characterized by persistent progression of fibrosis in the chronic phase. Pranlukast (30 mg/kg/day) was administered orally to mice for 2 or 10 weeks after intratracheal silica instillation. Results: Pranlukast treatment for 10 weeks significantly attenuated the progression of pulmonary fibrosis, and decreased the content of CysLTs and LTB₄, which were markedly increased in the bronchoalveolar lavage fluid (BALF) and lung tissues of silica-instilled mice in the chronic phase. However, pranlukast treatment for 2 weeks neither affected the acute inflammatory response induced by silica instillation nor inhibited the onset of fibrosis. The expression of TGF-β1 and TNF-α was not affected by pranlukast treatment for either 2 or 10 weeks. Conclusions: Pranlukast attenuates the progression of pulmonary fibrosis in the chronic phase but has no effect on the acute inflammatory response or on the onset of pulmonary fibrosis. The antifibrotic effect of pranlukast may be exhibited by antagonizing the direct profibrotic effect of CysLTs, without affecting the expression of other profibrotic cytokines such as TGF-β1 and TNF-α, and also by decreasing the production of CysLTs and LTB₄.

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Section: Discussionmentioning

confidence: 99%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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“…Upon in vitro stimulation with LPS, the secretion of these cyclooxygenase products was strongly enhanced [74]. In contrast, in vitro stimulation with silica enhanced production of metabolites of the lipoxygenase pathway and decreased the production of the products of the cyclooxygenase pathway [73]. From these in vitro data, one may assume that silica can increase arachidonic acid metabolites like LTB 4 which promote fibroblast proliferation in vitro [75], either directly or by stimulating the production of IL-1 [76] and TNF [77].…”

Section: Arachidonic Acid Metabolism In Alveolar Macrophagesmentioning

confidence: 97%

“…The pattern of activation with respect to arachidonic acid metabolism appears to depend on the kind of stimulus used. Whereas IFN-γ has only preactivating properties (at least at the low dosage tested) LPS has been shown to either preactivate macrophages to enhance release of the lipoxygenase product LTB 4 , or, at higher dosages, to directly activate alveolar macrophages to enhance release mainly of cyclo-oxygenase pathway products, such as thromboxane B 2 (TxB 2 ) and prostaglandin E 2 (PGE 2 ) [73].…”

Section: Arachidonic Acid Metabolism In Alveolar Macrophagesmentioning

confidence: 99%

Pulmonary macrophages

Rogers¹

1994

Eur Respir J

472

221

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Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Together with the submucosal glands, goblet cells secrete high molecular weight mucus glycoproteins (mucins), which confer upon the airway surface fluid the requisite biochemical and biophysical properties which determine the efficiency of entrapment and transportation of inhaled irritants, particles and micro-organisms. The diversity of glycosylation of airway mucins may be important in facilitating adherence of micro-organisms to mucus prior to mucociliary clearance. Other secretory products, including lipids and "small" glycoproteins, may also be produced by goblet cells. It is possible that goblet cells have the potential to produce markedly more mucus than do the glands. Mucins are tightly packed in the intracellular granules of the goblet cell. The morphology of these granules varies with fixation technique, and release of mucins may be via a combination of merocrine and apocrine secretion. Discharge of mucus is accomplished remarkably rapidly (tens of milliseconds) and vast quantities of mucus are released (size expansions from the granule of many hundredfold). Depending upon species and preparation, goblet cells discharge mucus in response to a wide variety of stimuli, including proteinases, irritant gases, inflammatory mediators, reactive oxygen species, nerve activation and changes in the biophysical environment. Under normal conditions, goblet cell proliferation and differentiation, particularly to ciliated cells, contributes to maintenance of the airway epithelial cell population. In addition to participating in acute airway defence, goblet cells increase in number in response to chronic airway insult, with a resultant increase in output of mucus. The increase in number of cells is via hyperplastic and metaplastic mechanisms. Early triggers for the development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways.

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“…Choi and colleagues [ 82 ] suggest that silica activates transcription of the human COX-2 gene through the induction of NF-kB activity. Moreover, eicosanoid levels measured after silica exposure reveal a significant increase in expression of PGE2 [ 83 , 84 ] and leukotriene B4 [ 84 ], but also C4, D4, and E4 expression [ 83 ], alongside a significant decrease in thromboxane B2 (TxB2) expression [ 83 , 84 ]. It should be noted that opposite results tend to be reported when surfactant is added with silica [ 84 ].…”

Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 99%

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

et al. 2022

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Silicon dioxide (SiO2) is a mineral compound present in the Earth’s crust in two mineral forms: crystalline and amorphous. Based on epidemiological and/or biological evidence, the pulmonary effects of crystalline silica are considered well understood, with the development of silicosis, emphysema, chronic bronchitis, or chronic obstructive pulmonary disease. The structure and capacity to trigger oxidative stress are recognized as relevant determinants in crystalline silica’s toxicity. In contrast, natural amorphous silica was long considered nontoxic, and was often used as a negative control in experimental studies. However, as manufactured amorphous silica nanoparticles (or nanosilica or SiNP) are becoming widely used in industrial applications, these paradigms must now be reconsidered at the nanoscale (<100 nm). Indeed, recent experimental studies appear to point towards significant toxicity of manufactured amorphous silica nanoparticles similar to that of micrometric crystalline silica. In this article, we present an extensive review of the nontumoral pulmonary effects of silica based on in vitro and in vivo experimental studies. The findings of this review are presented both for micro- and nanoscale particles, but also based on the crystalline structure of the silica particles.

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Modulation of eicosanoid production by human alveolar macrophages exposed to silica in vitro.

Cited by 17 publications

References 21 publications

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Pulmonary macrophages

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

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