scholarly journals Ferulic Acid Protects against Porcine Parvovirus Infection-Induced Apoptosis by Suppressing the Nuclear Factor-κB Inflammasome Axis and Toll-Like Receptor 4 via Nonstructural Protein 1

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Ma ◽  
Zhenhuan Guo ◽  
Zhiqiang Zhang ◽  
Xianghui Li ◽  
Yonglu Liu ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Nonstructural Protein ◽  
Placental Tissue ◽  
Nuclear Factor Κb ◽  
Inflammasome Activation ◽  
Porcine Parvovirus ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Nonstructural Protein 1 ◽  
Induced Apoptosis

Background. Porcine parvovirus (PPV) infection-induced apoptosis was recently identified as an important pathological factor in PPV-induced placental tissue damage, resulting in reproduction failure. In the present study, we demonstrate the possible involvement of toll-like receptor (TLR) 4 and nuclear factor (NF)-κB inflammasome activation in PPV infection-induced apoptosis and the protective potential of ferulic acid (FA). PPV infection significantly activated the expression levels of TLR4, NF-κB, MyD88, and interleukin (IL)-6. However, FA ameliorated the pathological process, prevented histological alterations, and inhibited the apoptosis rate in porcine kidney (PK-15) cells infected with PPV. Results. FA inhibited PPV infection-induced inflammasome activation as shown by decreases in the expression of NF-κB, MyD88, and IL-6. FA also downregulated nonstructural (NS) 1 protein expression in infected PK-15 cells. Conclusions. FA downregulated NS1 and TLR4 signaling, prevented the overproduction of reactive oxygen species, and suppressed the NF-κB inflammasome axis to inhibit PPV-induced apoptosis in PK-15 cells.

scholarly journals Porcine Parvovirus Infection Causes Pig Placenta Tissue Damage Involving Nonstructural Protein 1 (NS1)-Induced Intrinsic ROS/Mitochondria-Mediated Apoptosis

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 389 ◽  
Author(s):  
Zhang ◽  
Fan ◽  
Li ◽  
Liang ◽  
Huo ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Apoptosis ◽  
Nonstructural Protein ◽  
Placental Tissue ◽  
Reproductive Failure ◽  
Porcine Parvovirus ◽  
Nonstructural Protein 1 ◽  
Host Cell Apoptosis ◽  
Tissue Damages ◽  
Induced Apoptosis

Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that PPV nonstructural protein 1 (NS1) can induce host cell apoptosis and death, thereby indicating the NS1 may play a crucial role in PPV-induced placental tissue damages and reproductive failure. We have found that NS1-induced apoptosis was significantly inhibited by caspase 9 inhibitor, but not caspase 8 inhibitor, and transfection of NS1 gene into PK-15 cells significantly inhibited mitochondria-associated antiapoptotic molecules Bcl-2 and Mcl-1 expressions and enhanced proapoptotic molecules Bax, P21, and P53 expressions, suggesting that NS1-induced apoptosis is mainly through the mitochondria-mediated intrinsic apoptosis pathway. We also found that both PPV infection and NS1 vector transfection could cause host DNA damage resulting in cell cycle arrest at the G1 and G2 phases, trigger mitochondrial ROS accumulation resulting in mitochondria damage, and therefore, induce the host cell apoptosis. This study provides a molecular basis for elucidating PPV-induced cell apoptosis and reproductive failure.

scholarly journals CD4+CD25+Foxp3+ regulatory T cells regulate immune balance in unexplained recurrent spontaneous abortion via the Toll-like receptor 4/nuclear factor-κB pathway

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052098094
Author(s):  
Shuang Qin ◽  
Li Li ◽  
Jia Liu ◽  
Jinrui Zhang ◽  
Qing Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Tlr4 Antagonist

Objective The present study aimed to evaluate the effects of cluster of differentiation (CD)4+CD25+ forkhead box p3 (Foxp3)+ regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms. Methods The proportion of CD4+CD25+Foxp3+ Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide. Results The proportion of CD4+CD25+Foxp3+ Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4+CD25+Foxp3+ Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model. Conclusions These data suggest that CD4+CD25+Foxp3+ Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.

scholarly journals The Toll-like receptor 1/2 agonists Pam3CSK4 and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes

Immunology ◽  
2011 ◽  
Vol 134 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Nicholas T. Funderburg ◽  
Julie K. Jadlowsky ◽  
Michael M. Lederman ◽  
Zhimin Feng ◽  
Aaron Weinberg ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Interleukin 10 ◽  
Nuclear Factor ◽  
Human Monocytes ◽  
Toll Like Receptor

Tetramethylpyrazine protects lymphocytes from radiation-induced apoptosis through nuclear factor-κB

2014 ◽  
Vol 12 (10) ◽  
pp. 730-737 ◽  
Author(s):  
Xiao-Yan WANG ◽  
Zeng-Chun MA ◽  
Yu-Guang WANG ◽  
Hong-Ling TAN ◽  
Cheng-Rong XIAO ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Radiation Induced ◽  
Induced Apoptosis

scholarly journals DDX3 directly facilitates IKKα activation and regulates downstream signalling pathways

2018 ◽  
Vol 475 (22) ◽  
pp. 3595-3607 ◽  
Author(s):  
Anthony Fullam ◽  
Lili Gu ◽  
Yvette Höhn ◽  
Martina Schröder
Keyword(s):  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Type I Interferons ◽  
Signalling Pathways ◽  
Type I ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Disease States ◽  
Dead Box ◽  
Iκb Kinase

DDX3 is a DEAD-box RNA helicase that we and others have previously implicated in antiviral immune signalling pathways leading to type I interferon (IFN) induction. We previously demonstrated that it directly interacts with the kinase IKKε (IκB kinase ε), enhances it activation, and then facilitates phosphorylation of the transcription factor IRF3 by IKKε. However, the TLR7/9 (Toll-like receptor 7/9)-mediated pathway, one of the most physiologically relevant IFN induction pathways, proceeds independently of IKKε or the related kinase TBK1 (TANK-binding kinase 1). This pathway induces type I IFN production via the kinases NIK (NF-κB-inducing kinase) and IKKα and is activated when plasmacytoid dendritic cells sense viral nucleic acids. In the present study, we demonstrate that DDX3 also directly interacts with IKKα and enhances its autophosphorylation and -activation. Modulation of DDX3 expression consequently affected NIK/IKKα-mediated IRF7 phosphorylation and induction of type I interferons. In addition, alternative NF-κB (nuclear factor-κB) activation, another pathway regulated by NIK and IKKα, was also down-regulated in DDX3 knockdown cells. This substantially broadens the effects of DDX3 in innate immune signalling to pathways beyond TBK1/IKKε and IFN induction. Dysregulation of these pathways is involved in disease states, and thus, our research might implicate DDX3 as a potential target for their therapeutic manipulation.

scholarly journals Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

2009 ◽  
Vol 94 (1) ◽  
pp. 261-267 ◽  
Author(s):  
A. R. Baker ◽  
A. L. Harte ◽  
N. Howell ◽  
D. C. Pritlove ◽  
A. M. Ranasinghe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Inflammatory Profile ◽  
Artery Disease ◽  
And Control

Abstract Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P<0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

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