Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

Chen, Ying; Li, Cuiying; Wu, Dong; Song, Laiyu; Wen, Tao; Dai, Wujing; Yu, Yong; Liu, Fangwei; Zhao, Ming; Lu, Chun-Wei; Chen, Jie

doi:10.1016/j.taap.2013.11.012

Cited by 63 publications

(51 citation statements)

References 51 publications

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“…New evidence indicates that Th17 cells play an important pathogenic role in granuloma development in lung and liver [65]–[67]. Th17 pathway promotes tissue granulomatous inflammation through the activation of pro-inflammatory cytokine/chemokine release and the recruitment of neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Yakoub

Devosse

et al. 2014

PLoS ONE

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The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-β, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.

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Section: Discussionmentioning

confidence: 99%

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Yakoub

Devosse

et al. 2014

PLoS ONE

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“…Our study may have practical applications. For example, it has already documented that IL-17A neutralization may alleviate the early stage of silica-induced lung inflammation and delay its progression [25]. Quite recently, a bispecific anti-TNFα/IL-17 antibody showed superior efficacy in blocking inflammatory cytokine and chemokine responses in the culture of human fibroblast-like synoviocytes from rheumatoid arthritis, and that this antibody displayed a protective impact on the bone of arthritic mice [26].…”

Section: Discussionmentioning

confidence: 99%

Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases

Yuan²,

Zhu³

et al. 2016

Cell Physiol Biochem

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Aims: To clarify the imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases (AITDs) including Graves' disease(GD), Hashimoto's thyroiditis(HT) and Graves' ophthalmopathy (GO). Methods: 47 patients with AITD (including 16 GD, 15 HT, and 16 GO) and 12 healthy controls were enrolled in this study. The percentages of Th17 and Treg cells, the ratio of Th17/Treg, as well as their related transcription factors RORγt and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry and real-time quantitative PCR Results: Compared with those in control group, the percentage of CD4⁺IL-17⁺T cell(Th17) and the mRNA expression of its transcription factor RORγt were higher in PBMCs of AITDs (P<0.05), particularly in HT subgroup (P<0.01). The percentage of CD4⁺Foxp3⁺T (Treg) cells and its transcription factor Foxp3 mRNA were significantly decreased in PBMCs of GD (P<0.05). In addition, the ratio of Th17/Treg was elevated in AITD group and GO subgroup (P<0.01). In GO subgroup, the patients with clinical activity score (CAS) above 4.5 had higher percentages of Th17 than those with CAS ranging from 3 to 4.5 (P<0.05). Conclusion: Increased Th17 lymphocytes may play a more important role in the pathogenesis of HT and GO while decreased Treg may be greatly involved in GD.

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“…The content of free SiO 2 dust was 99%, and the particle size for 80% of the SiO 2 dust was between 1 and 5 μm. In addition, a number of research literatures recruited SiO 2 from this vender to establish the silicosis mice model, providing full descriptions of the properties of SiO 2 (Chen et al, ; Liu et al, ). Silica particulates were grinded for 1 hour and maintained at 180°C for 2 hours to dehydrate and remove endotoxin.…”

Section: Methodsmentioning

confidence: 99%

Comparative RNA‐Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model

Chen

Yao

et al. 2018

J of Applied Toxicology

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Silicosis is a long-established public health issue in developing countries due to increasingly serious air pollution and poorly implemented occupational safety regulation. Inhalation of silica triggers cytotoxicity, oxidative stress, pulmonary inflammation and eventually silicosis. Current understanding in the pathogenesis and mechanism of silicosis is limited, and no effective cure is clinically available once silicosis is developed. A number of studies were conducted to investigate silica-induced alternate gene expressions in pulmonary cells. However, transcriptome analysis in a silicosis animal model is needed. This study was performed to evaluate the transcriptional alternations in silicotic mice using comparative RNA-Seq. A silicosis mice model was established by intratracheal instillation of silica suspensions, and validated by histological examinations. High-throughput sequencing and differential gene expression analysis revealed 749 upregulated genes and 70 downregulated genes in the silicosis model. Genes related to immune cell interactions, immune cell responses and inflammation were significantly enriched. Cytokine-cytokine receptor interaction and downstream JAK-STAT signaling pathways were the most significantly enriched KEGG pathways. Reverse transcription-polymerase chain reaction analysis and immunohistochemistry were performed to validate further the differential expression patterns of representative genes. The reported results in this study provide the basis for elucidating the molecular mechanisms for silica-induced pulmonary inflammation and fibrosis, and support the prevention and treatment of silicosis.

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Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice

Cited by 63 publications

References 51 publications

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases

Comparative RNA‐Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model

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