The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis

Barbarin, Virginie; Nihoul, Aurélie; Misson, Pierre‐Damien; Arras, Mohammed; Delos, Monique; Leclercq, Isabelle; Lison, Dominique; Huaux, François

doi:10.1186/1465-9921-6-112

Cited by 96 publications

(90 citation statements)

References 54 publications

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“…Thus, it remains to be explained why chronic lung inflammation induced by silica is not directed by IL-17-producing T cells as it is during the earlier response. We demonstrated previously that long-term responses to silica in mice are strongly associated with the upregulation of suppressive cytokines, such as IL-10, which control, at least in part, the establishment of chronic inflammation (24,57). Thus, we can speculate that this anti-inflammatory response can control the proinflammatory activities of IL-17A, as demonstrated in several recent reports (13,(58)(59)(60).…”

Section: Discussionsupporting

confidence: 61%

“…Collectively, these data suggested that IL-17A and IL-17A-producing T cells play a significant role in the establishment of the early alveolitis induced by silica to stimulate the production of proinflammatory chemokines and cytokines. In this experimental model of silicosis, lung injury and neutrophil accumulation are not limited to day 3, but chronic and persistent inflammation develop with lung fibrosis (24). Therefore, we tested whether IL-17A plays a role in the chronic inflammatory lung responses induced by silica.…”

Section: Il-23p40 Produced By Macrophages Mediates Pulmonary Th17 Celmentioning

confidence: 99%

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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

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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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Section: Discussionsupporting

confidence: 61%

Section: Il-23p40 Produced By Macrophages Mediates Pulmonary Th17 Celmentioning

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

Self Cite

130

107

View full text Add to dashboard Cite

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“…Of these, alveolar macrophages (AM) are avidly phagocytic and readily ingest airborne particulate matter, bacteria, and viruses through various pattern recognition receptors (8,9). These stimuli may then result in cytokine and chemokine secretion that promotes recruitment of inflammatory cells, immune activation, and deposition of extracellular matrices (10). Phagocytosis of silica results in AM apoptosis and necrosis, with subsequent release of intracellular silica that may become involved in multiple ingestion-re-ingestion cycles, which perpetuates the disease process (11,12).…”

mentioning

confidence: 99%

Antigen-Presenting Cell Population Dynamics during Murine Silicosis

Beamer¹,

Holian²

2007

Am J Respir Cell Mol Biol

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Silicosis is an occupational lung disease resulting from the inhalation of silica particles over prolonged periods of time, which causes chronic inflammation and progressive pulmonary fibrosis. Alveolar macrophages (AM) are critical effector cells, while less is known about the role and function of pulmonary dendritic cells (DC) in silicosis. We hypothesize that a balance exists between the suppressive nature of AM and the stimulatory capacity of DC to regulate lung immunity, and that this equilibrium may be overcome by silica exposure in vivo. Our results demonstrate that in response to silica exposure, both the percent and absolute number of AM significantly decreased over time, with a concomitant significant increase in DC. Both AM and DC exhibited cellular activation in response to silica, indicated by increased expression of cell surface markers. In the absence of silica-induced AM apoptosis (TNFR 1/2-null and Gld mice), no change was observed in the percent or absolute number of either cell type. Furthermore, bone marrow-derived DC, but not bone marrow-derived macrophages, migrated from the alveoli into the lung parenchyma in response to silica, resulting in significantly increased numbers of activated T lymphocytes. Collectively, the results demonstrate that AM and DC are distinct antigen-presenting cells within the respiratory tract that respond to silica exposure in vivo in unique ways, with significant implications for immune reactivity of the lung in response to environmental pathogens.

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“…This leads to the development of fibrotic nodules that are similar to the lesions humans develop secondary to occupational dust exposure. The development of fibrosis in mice secondary to silica exposure is strain dependent and the fibrotic response is different in mice and rats (Barbarin et al, 2005). In rats exposure to silica induces a chronic and progressive inflammation that is accompanied by the over production of TNF-.…”

Section: Silicamentioning

confidence: 99%

Inflammation and Pulmonary Fibrosis

Crooks¹,

Aslam²,

Hart³

2012

Inflammatory Diseases - Immunopathology, Clinical and Pharmacological Bases

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The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis

Abstract: Background: It has been generally well accepted that chronic inflammation is a necessary component of lung fibrosis but this concept has recently been challenged.

Cited by 96 publications

References 54 publications

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

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

Antigen-Presenting Cell Population Dynamics during Murine Silicosis

Inflammation and Pulmonary Fibrosis

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