scholarly journals 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yihang Yang ◽  
Bo Pang ◽  
Zihao Liu ◽  
Jie Li ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Innate Immune Response ◽  
Diffusion Tensor ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Motor Dysfunction ◽  
Mass Spectrometry Analysis ◽  
Nigrostriatal System

Several in vitro studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly in vivo. This study was designed to study the neurotoxicity of TaClo in vivo by stereotactically injecting TaClo into the striatum of Wistar rats. After the TaClo injections, rats were subjected to an open field test, and their distance travelled and tracks showed decreasing trends over time. The results of liquid chromatography-mass spectrometry analysis showed that the motor dysfunction of the TaClo-treated rats was accompanied by reduced dopamine levels in the striatum. Based on the diffusion tensor imaging data, the apparent diffusion coefficient of the nigrostriatal pathway was significantly increased, and subsequent histological staining revealed the demyelination of nigrostriatal fibres after the TaClo treatment. TaClo induced a loss of tyrosine hydroxylase-positive cells in the substantia nigra compacta. Regarding the underlying mechanism, TaClo caused oxidative stress in the nigrostriatal system by increasing the production of reactive oxygen species and reducing the mitochondria membrane potential. Meanwhile, the elevated expression of Iba-1, TNF-α, IL-6, Cox-2, and iNOS indicated microglial activation and a strong innate immune response in the nigrostriatal system. In addition, activated caspase-3 levels were increased. Thus, both mitochondrial impairments and the innate immune response are involved in TaClo-induced neurotoxicity.

scholarly journals Ursodeoxycholic Acid (UDCA) Mitigates the Host Inflammatory Response during Clostridioides difficile Infection by Altering Gut Bile Acids

2020 ◽  
Vol 88 (6) ◽  
Author(s):  
Jenessa A. Winston ◽  
Alissa J. Rivera ◽  
Jingwei Cai ◽  
Rajani Thanissery ◽  
Stephanie A. Montgomery ◽  
...  
Keyword(s):  
Immune Response ◽  
Bile Acid ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Colonization Resistance ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile infection (CDI) is associated with increasing morbidity and mortality posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this enteric pathogen. Administration of the secondary bile acid ursodeoxycholic acid (UDCA; ursodiol) inhibits the life cycles of various strains of C. difficile in vitro, suggesting that the FDA-approved formulation of UDCA, known as ursodiol, may be able to restore colonization resistance against C. difficile in vivo. However, the mechanism(s) by which ursodiol is able to restore colonization resistance against C. difficile remains unknown. Here, we confirmed that ursodiol inhibits C. difficile R20291 spore germination and outgrowth, growth, and toxin activity in a dose-dependent manner in vitro. In a murine model of CDI, exogenous administration of ursodiol resulted in significant alterations in the bile acid metabolome with little to no changes in gut microbial community structure. Ursodiol pretreatment resulted in attenuation of CDI pathogenesis early in the course of disease, which coincided with alterations in the cecal and colonic inflammatory transcriptome, bile acid-activated receptors nuclear farnesoid X receptor (FXR) and transmembrane G-protein-coupled membrane receptor 5 (TGR5), which are able to modulate the innate immune response through signaling pathways such as NF-κB. Although ursodiol pretreatment did not result in a consistent decrease in the C. difficile life cycle in vivo, it was able to attenuate an overly robust inflammatory response that is detrimental to the host during CDI. Ursodiol remains a viable nonantibiotic treatment and/or prevention strategy against CDI. Likewise, modulation of the host innate immune response via bile acid-activated receptors FXR and TGR5 represents a new potential treatment strategy for patients with CDI.

scholarly journals Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress Are Independent of Their Interferon Activation

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 540 ◽  
Author(s):  
Sarah Zobel ◽  
Mechthild Lorenz ◽  
Giada Frascaroli ◽  
Janik Böhnke ◽  
Nicole Bilz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Innate Immune Response ◽  
Rubella Virus ◽  
Gene Activation ◽  
Innate Immune ◽  
Clinical Isolates ◽  
Stress Induction ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Ros

Rubella virus (RV) infection impacts cellular metabolic activity in a complex manner with strain-specific nutritional requirements. Here we addressed whether this differential metabolic influence was associated with differences in oxidative stress induction and subsequently with innate immune response activation. The low passaged clinical isolates of RV examined in this study induced oxidative stress as validated through generation of the reactive oxygen species (ROS) cytoplasmic hydrogen peroxide and mitochondrial superoxide. The addition of the cytoplasmic and mitochondrial ROS scavengers N-acetyl-l-cysteine and MitoTEMPO, respectively, reduced RV-associated cytopathogenicity and caspase activation. While the degree of oxidative stress induction varied among RV clinical isolates, the level of innate immune response and interferon-stimulated gene activation was comparable. The type III IFNs were highly upregulated in all cell culture systems tested. However, only pre-stimulation with IFN β slightly reduced RV replication indicating that RV appears to have evolved the ability to counteract innate immune response mechanisms. Through the data presented, we showed that the ability of RV to induce oxidative stress was independent of its capacity to stimulate and counteract the intrinsic innate immune response.

scholarly journals Effects of Regulatory T Cell Depletion on NK Cell Responses against Listeria monocytogenes in Feline Immunodeficiency Virus Infected Cats

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 984
Author(s):  
Simões ◽  
LaVoy ◽  
Dean
Keyword(s):  
Immune Response ◽  
Listeria Monocytogenes ◽  
Dendritic Cell ◽  
Innate Immune Response ◽  
Feline Immunodeficiency Virus ◽  
Innate Immune ◽  
Treg Depletion ◽  
Cell Responses ◽  
Immunodeficiency Virus

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with Listeria monocytogenes (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction.

scholarly journals The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression

Oncogene ◽  
2020 ◽  
Vol 39 (44) ◽  
pp. 6841-6855 ◽  
Author(s):  
Christina Jessen ◽  
Julia K. C. Kreß ◽  
Apoorva Baluapuri ◽  
Anita Hufnagel ◽  
Werner Schmitz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Transcription Factor ◽  
Prostaglandin E2 ◽  
Innate Immune Response ◽  
Stress Responses ◽  
Melanoma Cells ◽  
Innate Immune ◽  
Dependent Manner

AbstractThe transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H2O2 or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.

scholarly journals The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

2020 ◽  
Vol 8 (4) ◽  
pp. 479
Author(s):  
Valeria Garcia-Castillo ◽  
Guillermo Marcial ◽  
Leonardo Albarracín ◽  
Mikado Tomokiyo ◽  
Patricia Clua ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Helicobacter Pylori Infection ◽  
Beneficial Effects ◽  
Ifn Γ ◽  
H Pylori

Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.

Effects of triclocarban on oxidative stress and innate immune response in zebrafish embryos

Chemosphere ◽  
2018 ◽  
Vol 210 ◽  
pp. 93-101 ◽  
Author(s):  
Jiajing Wei ◽  
Ting Zhou ◽  
Zhiyong Hu ◽  
Ying Li ◽  
Hongfang Yuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Zebrafish Embryos

scholarly journals Leptospira interrogans Catalase Is Required for Resistance to H2O2and for Virulence

2012 ◽  
Vol 80 (11) ◽  
pp. 3892-3899 ◽  
Author(s):  
Azad Eshghi ◽  
Kristel Lourdault ◽  
Gerald L. Murray ◽  
Thanatchaporn Bartpho ◽  
Rasana W. Sermswan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Immune Response ◽  
Innate Immune Response ◽  
Reactive Oxygen ◽  
Innate Immune ◽  
Leptospira Interrogans ◽  
Oxygen Species ◽  
Content Type ◽  
Host Innate Immune Response

ABSTRACTPathogenicLeptospiraspp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterizedLeptospira interroganscatalase (KatE), the only annotated catalase found within pathogenicLeptospiraspecies, by assessing its role in resistance to H2O2-induced oxidative stress and during infection in hamsters. PathogenicL. interrogansbacteria had a 50-fold-higher survival rate under H2O2-induced oxidative stress than did saprophyticL. biflexabacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenicLeptospiraspecies. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation ofkatEin pathogenicLeptospirabacteria drastically diminished leptospiral viability in the presence of extracellular H2O2and reduced virulence in an acute-infection model. Combined, these results suggest thatL. interrogansKatE confersin vivoresistance to reactive oxygen species induced by the host innate immune response.

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