scholarly journals Amorphous silica nanoparticles (nSP50) exacerbate hepatic damage through the activation of acquired cell-mediated immunity

Nano Express ◽  
2022 ◽  
Author(s):  
Shun-ichi Eto ◽  
Kazuma Higashisaka ◽  
Aoi Koshida ◽  
Kenta Sato ◽  
Mao Ogura ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Plasma Levels ◽  
Biological Effects ◽  
Hepatic Damage ◽  
Acquired Immunity ◽  
Cell Mediated Immunity ◽  
Cd8 Cells ◽  
Immunodeficient Mice ◽  
Ifn Γ

Abstract Due to their innovative functions, the use of nanoparticles in various industries has been expanding. However, a key concern is whether nanoparticles induce unexpected biological effects. Although many studies have focused on innate immunity, information on whether nanoparticles induce biological responses through effects on acquired immunity is sparse. Here, to assess the effects of amorphous silica nanoparticles on acquired immunity, we analyzed changes in acute toxicities after pretreatment with amorphous silica nanoparticles (50 nm in diameter; nSP50). Pretreatment with nSP50 biochemically and pathologically exacerbated nSP50-induced hepatic damage in immunocompetent mice. However, pretreatment with nSP50 did not exacerbate hepatic damage in immunodeficient mice. Consistent with this, the depletion of CD8+ cells with an anti-CD8 antibody in animals pretreated with nSP50 resulted in lower plasma levels of hepatic injury markers such as ALT and AST after an intravenous administration than treatment with an isotype-matched control antibody. Finally, stimulation of splenocytes promoted the release of IFN-γ in nSP50-pretreated mice regardless of the stimulator used. Moreover, the blockade of IFN-γ decreased plasma levels of ALT and AST levels in nSP50-pretreated mice. Collectively, these data show that nSP50-induced acquired immunity leads to exacerbation of hepatic damage through the activation of cytotoxic T lymphocytes.

scholarly journals Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

2017 ◽  
Vol 24 (10) ◽  
Author(s):  
Giulia Malachin ◽  
Elisa Lubian ◽  
Fabrizio Mancin ◽  
Emanuele Papini ◽  
Regina Tavano
Keyword(s):  
Dendritic Cells ◽  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Content Type ◽  
E Coli ◽  
Synergistic Induction ◽  
Ifn Γ

ABSTRACT Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (Escherichia coli, Staphylococcus epidermidis) or pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) in the presence of amorphous silica nanoparticles (SiO2 NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. E. coli and S. epidermidis EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1β (IL-1β), IL-12, IL-10, and IL-6, while E. coli and S. epidermidis EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, and IL-5. On the contrary, S. aureus and P. aeruginosa EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO2 NP doses. DCs consistently supported the proliferation and differentiation of CD4+ and CD8+ T cells secreting IFN-γ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1β was prevalently mediated by proteins in the case of E. coli EMs and by nonproteins in the case of S. epidermidis EMs. A bacterial costimulus did not act on DCs after adsorption on SiO2 NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.

scholarly journals Repeated vs. Acute Exposure of RAW264.7 Mouse Macrophages to Silica Nanoparticles: A Bioaccumulation and Functional Change Study

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 215 ◽  
Author(s):  
Anaëlle Torres ◽  
Bastien Dalzon ◽  
Véronique Collin-Faure ◽  
Thierry Rabilloud
Keyword(s):  
Silica Nanoparticles ◽  
Cell Line ◽  
Amorphous Silica ◽  
Biological Effects ◽  
Functional Change ◽  
Repeated Exposure ◽  
Acute Exposure ◽  
Human Populations ◽  
No Production

Synthetic amorphous silica is used in various applications such as cosmetics, food, or rubber reinforcement. These broad uses increase human exposure, and thus the potential risk related to their short- and long-term toxicity for both consumers and workers. These potential risks have to be investigated, in a global context of multi-exposure, as encountered in human populations. However, most of the in vitro research on the effects of amorphous silica has been carried out in an acute exposure mode, which is not the most relevant when trying to assess the effects of occupational exposure. As a first step, the effects of repeated exposure of macrophages to silica nanomaterials have been investigated. The experiments have been conducted on in vitro macrophage cell line RAW264.7 (cell line from an Abelson murine leukemia virus-induced tumor), as this cell type is an important target cell in toxicology of particulate materials. The bioaccumulation of nanomaterials and the persistence of their effects have been studied. The experiments carried out include the viability assay and functional tests (phagocytosis, NO and reactive oxygen species dosages, and production of pro- and anti-inflammatory cytokines) using flow cytometry, microscopy and spectrophotometry. Accumulation of silica nanoparticles (SiO2 NP) was observed in both exposure scenarii. However, differences in the biological effects between the exposure scenarii have also been observed. For phagocytosis, NO production and Tumor Necrosis Factor (TNF) release, repeated exposure tended to induce fewer effects than acute exposure. Nevertheless, repeated exposure still induces alterations in the macrophage responses and thus represents a scenario to be tested in detail.

scholarly journals Silica nanoparticles are less toxic to human lung cells when deposited at the air–liquid interface compared to conventional submerged exposure

2014 ◽  
Vol 5 ◽  
pp. 1590-1602 ◽  
Author(s):  
Alicja Panas ◽  
Andreas Comouth ◽  
Harald Saathoff ◽  
Thomas Leisner ◽  
Marco Al-Rawi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Particle Deposition ◽  
Biological Effects ◽  
Cellular Responses ◽  
Liquid Interface ◽  
Lung Cells ◽  
Air Liquid Interface ◽  
Submerged Conditions

Background: Investigations on adverse biological effects of nanoparticles (NPs) in the lung by in vitro studies are usually performed under submerged conditions where NPs are suspended in cell culture media. However, the behaviour of nanoparticles such as agglomeration and sedimentation in such complex suspensions is difficult to control and hence the deposited cellular dose often remains unknown. Moreover, the cellular responses to NPs under submerged culture conditions might differ from those observed at physiological settings at the air–liquid interface. Results: In order to avoid problems because of an altered behaviour of the nanoparticles in cell culture medium and to mimic a more realistic situation relevant for inhalation, human A549 lung epithelial cells were exposed to aerosols at the air–liquid interphase (ALI) by using the ALI deposition apparatus (ALIDA). The application of an electrostatic field allowed for particle deposition efficiencies that were higher by a factor of more than 20 compared to the unmodified VITROCELL deposition system. We studied two different amorphous silica nanoparticles (particles produced by flame synthesis and particles produced in suspension by the Stöber method). Aerosols with well-defined particle sizes and concentrations were generated by using a commercial electrospray generator or an atomizer. Only the electrospray method allowed for the generation of an aerosol containing monodisperse NPs. However, the deposited mass and surface dose of the particles was too low to induce cellular responses. Therefore, we generated the aerosol with an atomizer which supplied agglomerates and thus allowed a particle deposition with a three orders of magnitude higher mass and of surface doses on lung cells that induced significant biological effects. The deposited dose was estimated and independently validated by measurements using either transmission electron microscopy or, in case of labelled NPs, by fluorescence analyses. Surprisingly, cells exposed at the ALI were less sensitive to silica NPs as evidenced by reduced cytotoxicity and inflammatory responses. Conclusion: Amorphous silica NPs induced qualitatively similar cellular responses under submerged conditions and at the ALI. However, submerged exposure to NPs triggers stronger effects at much lower cellular doses. Hence, more studies are warranted to decipher whether cells at the ALI are in general less vulnerable to NPs or specific NPs show different activities dependent on the exposure method.

HCA587 protein vaccine induces specific antitumor immunity mediated by CD4+ T-cells expressing granzyme B in a mouse model of melanoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Weiming Yang ◽  
Weiheng Zhang ◽  
Xiaozhong Wang ◽  
Liming Tan ◽  
Hua Li ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Effect ◽  
Granzyme B ◽  
Cell Subset ◽  
Cell Mediated Immunity ◽  
Protein Vaccine ◽  
Tumor Tissues ◽  
Wide Range ◽  
Ifn Γ

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.

Association of microRNA-125a with the clinical features, disease activity and inflammatory cytokines of juvenile-onset lupus patients

Lupus ◽  
2021 ◽  
pp. 096120332110103
Author(s):  
Eman Eissa ◽  
Botros Morcos ◽  
Rania Fawzy Mahmoud Abdelkawy ◽  
Hanan H Ahmed ◽  
Naglaa M Kholoussi
Keyword(s):  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Plasma Levels ◽  
Clinical Manifestations ◽  
Juvenile Onset ◽  
Expression Levels ◽  
Ifn Γ ◽  
Chronic Autoimmune Disease ◽  
Normal Controls

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile-onset SLE (jSLE) exhibits an aggressive clinical phenotype and severe complications. Dysregulated expression of microRNAs (miRs) in immune cells from patients with SLE has been found. We aim to evaluate the association of miR-125a with the clinical and laboratory characteristics, disease activity and inflammatory cytokines of jSLE patients. Methods 60 jSLE patients and 25 normal controls were involved in the study. The expression pattern of miR-125a was determined in plasma of all subjects using qRT-PCR. In addition, plasma levels of IL-17 and IFN-γ were examined using ELISA. The correlation of miR-125a expression with the clinical manifestations and disease activity of jSLE patients was analyzed. Also, its association with the inflammatory cytokines was investigated in jSLE patients. Results Our findings showed that miR-125a expression levels were significantly reduced in jSLE patients compared to normal controls ( p < 0.01) and these expression levels differed based on the clinical variability of patients. In addition, plasma levels of IL-17 and IFN-γ in jSLE patients were significantly higher than healthy controls ( p < 0.01). Finally, miR-125a expression had significant negative associations with each of SLEDAI-2K ( p < 0.01), SLICC ( p < 0.01), ESR ( p < 0.05), proteinuria ( p < 0.01) and IL-17 levels ( p < 0.01) in jSLE patients. Conclusion Our findings postulate that miR-125a could act as a candidate therapeutic target for its possible regulation of inflammation in jSLE patients.

scholarly journals Insights on toxicity, safe handling and disposal of silica aerogels and amorphous nanoparticles

2021 ◽  
Author(s):  
João P. Vareda ◽  
Carlos A. García-González ◽  
Artur J. M. Valente ◽  
Rosana Simón-Vázquez ◽  
Marina Stipetic ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Silica Aerogels ◽  
Safe Handling ◽  
Synthetic Amorphous Silica ◽  
Amorphous Nanoparticles

The toxicity and ecotoxicity effects, handling and disposal of synthetic amorphous silica nanoparticles and aerogels are reviewed and discussed.

scholarly journals Are Biogenic and Pyrogenic Mesoporous SiO2 Nanoparticles Safe for Normal Cells?

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1427
Author(s):  
Katarzyna Solarska-Ściuk ◽  
Kinga Adach ◽  
Sylwia Cyboran-Mikołajczyk ◽  
Dorota Bonarska-Kujawa ◽  
Agnieszka Rusak ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Biological Effects ◽  
Mesoporous Silica Nanoparticles ◽  
Volume Ratio ◽  
Sio2 Nanoparticles ◽  
Amorphous Structure ◽  
Intracellular Ros ◽  
Materials Used ◽  
The Impact

Silicon dioxide, in the form of nanoparticles, possesses unique physicochemical properties (size, shape, and a large surface to volume ratio). Therefore, it is one of the most promising materials used in biomedicine. In this paper, we compare the biological effects of both mesoporous silica nanoparticles extracted from Urtica dioica L. and pyrogenic material. Both SEM and TEM investigations confirmed the size range of tested nanoparticles was between 6 and 20 nanometers and their amorphous structure. The cytotoxic activity of the compounds and intracellular ROS were determined in relation to cells HMEC-1 and erythrocytes. The cytotoxic effects of SiO2 NPs were determined after exposure to different concentrations and three periods of incubation. The same effects for endothelial cells were tested under the same range of concentrations but after 2 and 24 h of exposure to erythrocytes. The cell viability was measured using spectrophotometric and fluorimetric assays, and the impact of the nanoparticles on the level of intracellular ROS. The obtained results indicated that bioSiO2 NPs, present higher toxicity than pyrogenic NPs and have a higher influence on ROS production. Mesoporous silica nanoparticles show good hemocompatibility but after a 24 h incubation of erythrocytes with silica, the increase in hemolysis process, the decrease in osmotic resistance of red blood cells, and shape of erythrocytes changed were observed.

Cellular internalization and stress response of ingested amorphous silica nanoparticles in the midgut of Drosophila melanogaster

2013 ◽  
Vol 1830 (1) ◽  
pp. 2256-2266 ◽  
Author(s):  
Ashutosh Pandey ◽  
Swati Chandra ◽  
Lalit Kumar Singh Chauhan ◽  
Gopeshwar Narayan ◽  
Debapratim Kar Chowdhuri
Keyword(s):  
Drosophila Melanogaster ◽  
Stress Response ◽  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Cellular Internalization

scholarly journals Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

2006 ◽  
Vol 75 (3) ◽  
pp. 1154-1166 ◽  
Author(s):  
Laura H. Hogan ◽  
Dominic O. Co ◽  
Jozsef Karman ◽  
Erika Heninger ◽  
M. Suresh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bacterial Load ◽  
Granulomatous Inflammation ◽  
Cd8 T Cell ◽  
Activated T Cells ◽  
Immunodeficient Mice ◽  
Ifn Γ

ABSTRACT The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.

Sign in / Sign up

Export Citation Format

Share Document