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Comparison of gene expression in BMDCs stimulated with gamma-PGA nanoparticles, LPS and unparticulate gamma-PGA

ABSTRACT: The gene expression levels in murine bone marrow-derived dendritic cells treated with γ-PGA NPs were examined by oligonucleitide microarray and compared with those in the cells treated with other adjuvants. The gene expression of proinflammatory chemokines, cytokines, and costimulatory molecules was upregulated considerably in DCs treated with γ-PGA NPs. The upregulation pattern was similar to that in DCs treated with LPS but not in DCs treated with unparticulate γ-PGA. The activation of DCs by γ-PGA NPs was confirmed by real-time RT-PCR analysis for the genes related to TLR signaling. The effect of γ-PGA NPs on DCs was not annihilated by treating with polymixin B, an inhibitor of LPS. Furthermore, the immunization of mice with γ-PGA NPs carrying OVA significantly induced Ag-specific CD8+ T cells and Ag-specific production of IL-2, TNF-α, and IFN-γ from the cells. Such activities of γ-PGA NPs were more prominent, when compared to the immunization with OVA plus aluminum hydroxide or OVA plus CFA. These results suggest that γ-PGA NPs induce a CD8+ T cell response through activating innate immunity in a fashion different from that of LPS. Thus, γ-PGA NPs may be an attractive adjuvant to be further developed for vaccine therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE15087 | GEO | 2009/03/05

SECONDARY ACCESSION(S): PRJNA114787

REPOSITORIES: GEO

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Time-course of gene expression in BMDCs stimulated with gamma-PGA nanoparticles

Project description:The gene expression levels in murine bone marrow-derived dendritic cells treated with γ-PGA NPs were examined by oligonucleitide microarray at 6, 12 and 24 hours. The gene expression of proinflammatory chemokines, cytokines, and costimulatory molecules was upregulated considerably in DCs treated with γ-PGA NPs at 6 hours.

2009-03-05 | GSE15089 | GEO

Waterborne exposure of adult zebrafish to silver nanoparticles and ionic silver results in silver accumulation and effects at cellular and molecular levels

Project description:Effects of silver nanoparticles (Ag NPs) on freshwater species have been reported in several studies, but there is not information on the potential long-term consequences of a previous exposure. In this work, we investigated the long-term effects of maltose-coated Ag NPs (20 nm) and of ionic silver (10 µg/L) after 21 days of exposure and at 6 months post-exposure (mpe) in adult zebrafish. Exposure resulted in significant silver accumulation in the whole body of fish exposed to ionic silver, but not in those exposed to Ag NPs. However, autometallography revealed metal accumulation in the liver and intestine of fish treated with the two silver forms and especially in the intestine of fish exposed to Ag NPs. X-ray microanalysis showed the presence of silver in gills, liver and intestine and of Ag NPs in gill and liver cells. Inflammation and hyperplasia were evident in the gills after both treatments and these histopathological conditions remained at 6 mpe. According to the hepatic transcriptome analysis, at 3 days ionic silver regulated a larger number of transcripts (410) than Ag NPs (129), while at 21 days Ag NPs provoked a stronger effect (799 vs 165 regulated sequences). Gene ontology terms such as “metabolic processes” and “response to stimulus” appeared enriched after all treatments, while “immune system” or “reproductive processes” were specifically enriched after the exposure to Ag NPs. This suggests that the toxicity of Ag NPs may not be solely related to the release of Ag ions, but also to the NP form. No evident effects were found on protein oxidation or on hepatocyte lysosomal membrane stability during exposure, but effects recorded on liver lysosomes and persistent damage on gill tissue at 6 mpe could indicate potential for long-term effects in exposed fish.

2018-06-12 | GSE89653 | GEO

Epigenetic effects of silver nanoparticles and ionic silver in Tetrahymena thermophila

Project description:The widespread use of silver nanoparticles (Ag NPs) has raised substantial health risks to environmental and human beings. Although various negative effects had been reported, little is known about the epigenetic toxicity induced by Ag+ and Ag NPs. This study characterized physiological and lncRNA profiles to explore the toxic effects and epigenetic mechanisms in Tetrahymena thermophila on exposure to Ag+ and three types of Ag NPs. We found that both of Ag+ and Ag NPs exhibited strong growth-inhibiting effects on T. thermophila. The toxicity was mainly caused by high levels of reactive oxygen species (ROS), which subsequently led to lipid peroxidation and mitochondrial dysfunction. As a defense mechanism against oxidative stress, the protist elicited an antioxidant response. Importantly, 1250 lncRNAs were differentially expressed under Ag+ or Ag NPs exposure relative to the non-exposure control, which were clustered into 15 expression modules in weighted gene co-expression network analysis. These gene modules exhibited toxicant-specific expression patterns, indicating that they play various regulatory roles, including cell growth inhibition, cell membrane cation channel activation, and oxidoreductase activity promotion. Taken together, this research illuminates how post-transcriptional mechanisms of a ciliated protozoa regulate responses to Ag+ and Ag NPs toxicities.

2021-09-10 | GSE157616 | GEO

Inhibition of γ-glutamyl transpeptidase suppresses LPS induced asthma exacerbation in a mouse model

Project description:To investigate the role of γ-glutamyltranspeptidase in severe asthma, we established an OVA/ LPS-induced asthma model. Inflammation analysis and second-generation sequencing revealed the mechanism by which inhibition of γ-glutamyltranspeptidase inhibited LPS-induced asthma exacerbation in mice.

2023-07-05 | GSE217834 | GEO

Sorted B cells from mice treated with MPL and/or R837

Project description:Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence suggests that activate dendritic cells (DCs) via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates DCs via multiple TLRs to stimulate pro-inflammatory cytokines. Triggering specific combinations of TLRs in DCs can induce synergistic production of cytokines, which results in enhanced T cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that programs such antibody responses remains a major challenge in vaccinology. We demonstrated that immunization of mice with synthetic nanoparticles containing antigens plus Toll-like receptor (TLR) ligands 4 (MPL) + 7 (R837) induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with a single TLR ligand. To determine whether there was any early programming of B cells, we isolated isotype switched, TCRbeta-CD11b-CD19+IgD-IgG+ B cells by FACS at 7 days post immunization with nanoparticles containing various adjuvants plus OVA, and performed microarray analyses to assess their molecular signatures. Two independent sets of samples at day 7 post-treatment were used in our analyses. Each set is comprised by B-cells from mice treated with MPL + R837 or from those treated with either individual MPL or R837 alone.

2010-12-01 | E-GEOD-25677 | biostudies-arrayexpress

Mus musculus

Project description:Comparison of gene expression in BMDCs stimulated with gamma-PGA nanoparticles, LPS and unparticulate gamma-PGA

| PRJNA114787 | ENA

Peptostreptococcaceae bacterium pGA-8

Project description:Peptostreptococcaceae bacterium pGA-8 Genome sequencing

| PRJNA254889 | ENA

Silver Nanoparticles Induce a Triclosan-Like Antibacterial Action Mechanism in Multi-Drug Resistant Klebsiella pneumoniae

Project description:Infections associated with antimicrobial-resistant bacteria now represent a significant threat to human health using conventional therapy, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles (Ag NPs) have been proposed as potential antimicrobial agents to combat infections. A complete understanding of their antimicrobial activity is required before these molecules can be used in therapy. Lysozyme coated Ag NPs were synthesized and characterized by TEMEDS, XRD, UV-vis, FTIR spectroscopy, zeta potential, and oxidative potential assay. Biochemical assays and deep level transcriptional analysis using RNA sequencing were used to decipher how Ag NPs exert their antibacterial action against multi-drug resistant Klebsiella pneumoniae MGH78578. RNAseq data revealed that Ag NPs induced a triclosan-like bactericidal mechanism responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released AgC generated oxidative stress both extra and intracellularly in K. pneumoniae. The data showed that triclosan-like activity and oxidative stress cumulatively underpinned the antibacterial activity of Ag NPs. This result was confirmed by the analysis of the bactericidal effect of Ag NPs against the isogenic K. pneumoniae MGH78578 1soxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Silver nanoparticles induce a triclosan like antibacterial action mechanism in multi-drug resistant K. pneumoniae. This study extends our understanding of anti-Klebsiella mechanisms associated with exposure to Ag NPs. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy.

2021-01-31 | GSE151953 | GEO

Streptococcus equinus strain:pga-7

Project description:Streptococcus equinus pGA-7 genome sequencing

| PRJNA303259 | ENA

Transcription profiling of mouse spleen after immunized using LPS vs MPL as adjuvant.

Project description:An unresolved issue in immunology is the extent to which inflammatory effects are needed for robust T cell responses. In this study, mice were immunized by iv injection using either high toxicity lipopolysaccharide (LPS) or low toxicity monophosphoryl lipid A (MPL) as adjuvant. Six hours after iv immunization, whole spleens were harvested and gene expression was measured in unfractionated splenic populations of cells. The analysis indicated that the low toxicity adjuvanticity of MPL was associated with TLR4-mediated signaling that was biased to the TRIF branch of TLR4, while LPS generated balanced MyD88 and TRIF-associated outcomes. Experiment Overall Design: B6.SJL mice adoptively transferred with T cells from B6.OTI and OTII transgenic TCR transgenic were immunized via intravenous injection with ova peptides alone ("Ova"), or with LPS ("OvaLPS") or MPL as adjuvant ("OvaMPL"). Six hours after immunization, the mice were euthanized by cervical dislocation, the spleens were removed and immediately lysed in guanidium chloride, and kept frozen until being used to extract total cellular RNA. Three mice each were given the indicated treatments, with independent processing and analysis of nine samples total.

2008-06-15 | E-GEOD-7768 | biostudies-arrayexpress

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