Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma

Ronzani, Carole; Casset, A.; Pons, Ferrán

doi:10.1007/s00204-013-1116-3

Cited by 48 publications

(47 citation statements)

References 56 publications

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“…25 In particular, oxidative stress has been proposed as the possible underlying mechanism by which CNTs exacerbate asthma in animal studies. 22,23,50 Indeed, the observed oxidative stress response was more pronounced in asthmatic tissues, thus further supporting the in vivo observations. Analysis of -the IL-8 expression, a critical airway epithelialderived (pro-)inflammatory chemokine primarily implicated in acute inflammation and accumulation of neutrophils in inflammatory diseases, 51 revealed an increase in both healthy and asthmatic MWCNT-exposed cells (Figure 6a).…”

Section: Resultssupporting

confidence: 83%

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

et al. 2017

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Although acute pulmonary toxicity of carbon nanotubes (CNTs) has been extensively investigated, the knowledge of potential health effects following chronic occupational exposure is currently limited and based only upon in vivo approaches. Our aim was to realistically mimic subchronic inhalation of multiwalled CNTs (MWCNTs) in vitro, using the air−liquid interface cell exposure (ALICE) system for aerosol exposures on reconstituted human bronchial tissue from healthy and asthmatic donors. The reliability and sensitivity of the system were validated using crystalline quartz (DQ12), which elicited an increased (pro-)inflammatory response, as reported in vivo. At the administrated MWCNT doses relevant to human occupational lifetime exposure (10 μg/cm 2 for 5 weeks of repeated exposures/5 days per week) elevated cilia beating frequency (in both epithelial cultures), and mucociliary clearance (in asthmatic cells only) occurred, whereas no cytotoxic reactions or morphological changes were observed. However, chronic MWCNT exposure did induce an evident (pro-)inflammatory and oxidative stress response in both healthy and asthmatic cells. The latter revealed stronger and more durable long-term effects compared to healthy cells, indicating that individuals with asthma may be more susceptible to adverse effects from chronic MWCNT exposure. Our results highlight the power of occupationally relevant subchronic exposures on human in vitro models in nanosafety hazard assessment. KEYWORDS: in vitro primary lung system, reconstituted healthy and asthma tissue, air−liquid interface, multiwalled carbon nanotubes, subchronic repeated exposure, occupational doses, hazard assessment T he high aspect ratio, excellent strength, and good conductivity offered by carbon nanotubes (CNTs) has raised their demand in the global industry market.

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Section: Resultssupporting

confidence: 83%

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

et al. 2017

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“…Further, JAG1 silencing inhibited the differentiation of Th2 cells and promoted the differentiation of Th1 cells. Consistent with the previous reports, JAG1 promoted Th2 differentiation on dendritic cells [23]. The Th1/Th2 balance plays an important role in the AHR.…”

Section: Discussionsupporting

confidence: 92%

Bronchial Epithelial Cells Promote the Differentiation of Th2 Lymphocytes in Airway Microenvironment through Jagged/Notch-1 Signaling after RSV Infection

Qin¹,

Qiu²,

Wu³

et al. 2019

Int Arch Allergy Immunol

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Background: The aim of this study was to investigate the role of Notch-1 signaling through Notch-1 ligands on bronchial epithelial cells (BECs) in regulating the development of T helper 2 (Th2) lymphocytes after RSV infection. Methods: Firstly, we analyzed the expression of cytokines and Notch-1 ligands in BECs by using real-time PCR. Then, RSV-infected BECs were co-cultured with CD4⁺ T cells in a transwell chamber for 48 h, and differentiation of T cells in the lower chamber was determined using flow cytometry and real-time PCR. JAG1 siRNA was then used to determine the effects of Jagged/Notch-1 signaling on the differentiation of Th2. An RSV-infected mouse model was also used to analyze the secretion of Th differentiation-associated cytokines in serum and lung tissues using ELISA, the histopathological changes using HE staining, and the expression of JAG1 and JAG2 in BECs. Results: The results showed that RSV promoted the expression of Th2-type cytokines and Jagged-1 and inhibited the expression of Jagged-2 in normal BECs. RSV-infected BECs induced Th2 differentiation. In addition, JAG1 downregulation inhibited the differentiation of Th2 and promoted differentiation of Th1. In the RSV-infected mouse model, the RSV titer, inflammation decreased with time. IL-4 and IL-17 increased on day 28 and 60, while IFNγ increased on day 7 and 28. Moreover, the expression of Jagged-1 increased and that of Jagged-2 decreased in BECs, which was consistent with IL-4 production in lung tissues. Conclusion: Our data showed that BECs had the potential to promote the differentiation of Th2 lymphocytes through Jagged-1/Notch-1 signaling.

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“…Several studies have shown that CNT fibers have adjuvant capacity as they aggravate allergen-induced airway inflammation [11-13,15,16]. Here, we investigated whether CNT have the ability to induce characteristics similar to allergic airway inflammation in healthy mice.…”

Section: Discussionmentioning

confidence: 98%

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

et al. 2014

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BackgroundCarbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.MethodsWe exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.ResultsHere we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.ConclusionsThese observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0048-2) contains supplementary material, which is available to authorized users.

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Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma

Cited by 48 publications

References 56 publications

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

Bronchial Epithelial Cells Promote the Differentiation of Th2 Lymphocytes in Airway Microenvironment through Jagged/Notch-1 Signaling after RSV Infection

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

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