scholarly journals An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

2018 ◽  
Author(s):  
Leon Strzadala ◽  
Anna Fiedorowicz ◽  
Edyta Wysokinska ◽  
Ewa Ziolo ◽  
Małgorzata Grudzien ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Mouse Models ◽  
Inhibitory Activity ◽  
Protein Level ◽  
Interferon Beta ◽  
The Other ◽  
Poly I:C ◽  
Double Stranded Rna ◽  
Inducible Protein ◽  
Toxic Concentrations

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2’,3’-e][1,4]thiazine (DQT) has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB were not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C) as well as in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4-8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in pathogenesis of autoimmune diseases.

scholarly journals An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2443 ◽  
Author(s):  
Leon Strzadala ◽  
Anna Fiedorowicz ◽  
Edyta Wysokinska ◽  
Ewa Ziolo ◽  
Małgorzata Grudzień ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Mouse Models ◽  
Inhibitory Activity ◽  
Protein Level ◽  
The Other ◽  
Poly I:C ◽  
Interferon Β ◽  
Double Stranded Rna ◽  
Inducible Protein ◽  
Toxic Concentrations

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2′,3′-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB was not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C), nor in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and that its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4–8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in the pathogenesis of autoimmune diseases.

scholarly journals Bridging autoinflammatory and autoimmune diseases

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Emad M. El-Shebiny ◽  
Enas S. Zahran ◽  
Sabry A. Shoeib ◽  
Eman S. Habib
Keyword(s):  
Innate Immunity ◽  
T Lymphocytes ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
High Titre ◽  
The Other ◽  
Clinical Spectrum ◽  
Autoinflammatory Diseases ◽  
Main Body ◽  
B And T Lymphocytes

Abstract Background Autoimmunity is used to cause by impairment of adaptive immunity alone, whereas autoinflammatory was originally defined as a consequence of unregulated innate immunity. So, the pathogenetic mechanisms of autoimmune diseases were well-thought-out to be mediated by B and T lymphocytes. Whereas, autoinflammatory diseases were defined as unprovoked times of inflammation with the absence of a high titre of autoantibodies. Main body of the abstract Autoimmune and autoinflammatory diseases were split into two groups, but considering the similarities, it can be considered as only one group of diseases with a large immune pathological and clinical spectrum which involves at one end pure autoimmune diseases and the other pure autoinflammatory diseases. Conclusions We can safely conclude that there is bridging between autoinflammatory and autoimmune diseases.

Immune responses of porcine airway epithelial cells to poly(I:C), a synthetic analogue of viral double-stranded RNA

2015 ◽  
Vol 95 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Xiu-qin Yang ◽  
Liang Wang ◽  
Hai-tao Li ◽  
Di Liu
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Digital Gene Expression ◽  
Enrichment Analysis ◽  
Airway Epithelial Cells ◽  
Poly I:C ◽  
Synthetic Analogue ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Double Stranded Rna

Yang, X.-q., Wang, L., Li, H.-t. and Liu, D. 2015. Immune responses of porcine airway epithelial cells to poly(I:C), a synthetic analogue of viral double-stranded RNA. Can. J. Anim. Sci. 95: 13–20. Swine respiratory disease (SRD) is one of the most economically important diseases affecting the pig industry. The main infectious agents that cause SRD are viruses, but the molecular pathogenesis of viral SRD has not been extensively studied. Here, using digital gene expression tag profiling, the global transcriptional responses to poly(I:C), a synthetic analogue of viral double-stranded RNA, was analyzed in porcine airway epithelial cells (PAECs). The profiling analysis revealed numerous differentially expressed genes (DEGs), including unknown sequences in the porcine nucleotide databases. Gene ontology enrichment analysis showed that DEGs were mainly enriched in response to stress (GO: 0006950), of which, defense response is one sub-process. Poly(I:C) challenge induced a general inflammation response as indicated by marked upregulation of a variety of pathogen recognition receptors, interferon-stimulated genes, proinflammatory cytokines, and chemokines, together with the significant downregulation of anti-inflammatory molecules. Furthermore, the antiapoptotic pathway was triggered, as demonstrated by the significant suppression of molecules involved in the induction of apoptosis, together with the significant stimulation of putative inhibitor of apoptosis. The results indicate that PAECs initiated defense against poly(I:C) challenge through the inflammation responses, whereas poly(I:C) can utilize antiapoptotic pathway to evade host defense.

Precipitin Inhibition of Candida stellatoidea Antiserum with Oligosaccharides Obtained from the Parent Mannan

1970 ◽  
Vol 1 (1) ◽  
pp. 61-63
Author(s):  
William O. Mitchell ◽  
H. F. Hasenclever
Keyword(s):  
Inhibitory Activity ◽  
The Other ◽  
Antigenic Determinants ◽  
Effective Inhibitor ◽  
Structural Configuration ◽  
Immune Precipitation

Inhibition of immune precipitation with oligosaccharides obtained from Candida stellatoidea mannan has been used to provide more information about the haptenic groups of this serologically active polysaccharide. The oligosaccharides di-, tri-, tetra-, and a mixture of penta- and hexasaccharides were studied. The inhibitory activity of these materials was tested with two immune sera. With one serum, 0.8 μmole of the mixture of penta- and hexasaccharides inhibited the reaction by 87%, and, with the other serum, 0.4 μmole of the mixture inhibited the reaction by 99%. Monosaccharides were also tested with each antiserum and found to be noninhibitory. It is apparent that the mixture of oligosaccharides containing 5 to 6 mannose units was the most effective inhibitor. Since it is known that these oligosaccharides contain a predominance of α 1-2 linkages and lesser numbers of α 1-3 linkages, it is likely that these are important in the structural configuration of the antigenic determinants.

MEK/ERK MAP kinase limits poly I:C‐induced antiviral gene expression in RAW264.7 macrophages by reducing interferon‐beta expression

FEBS Letters ◽  
2021 ◽  
Author(s):  
Shawn M. Freed ◽  
Danielle S. Baldi ◽  
Jason A. Snow ◽  
Sierra Athen ◽  
Zachary P. Guinn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Interferon Beta ◽  
Poly I:C ◽  
Raw264.7 Macrophages ◽  
Antiviral Gene

scholarly journals Acetylcholinesterase and Butyrylcholinesterase Inhibitory Compounds from Corydalis Cava (Fumariaceae)

2011 ◽  
Vol 6 (5) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Jakub Chlebek ◽  
Kateřina Macáková ◽  
Lucie Cahlíková ◽  
Milan Kurfürst ◽  
Jiří Kuneš ◽  
...  
Keyword(s):  
Human Blood ◽  
Inhibitory Activity ◽  
Potent Inhibitor ◽  
The Other ◽  
Spectroscopic Techniques ◽  
Dependent Manner ◽  
Isoquinoline Alkaloids ◽  
Chemical Structures ◽  
Inhibitory Compounds ◽  
Dose Dependent

Tubers of Corydalis cava were extracted with ethanol and fractionated using n-hexane, chloroform and ethanol. Repeated column chromatography, preparative TLC and crystallization led to the isolation of fifteen isoquinoline alkaloids. The chemical structures of the isolated compounds were determined on the basis of spectroscopic techniques and by comparison with literature data. All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. (+)-Canadaline inhibited acetylcholinesterase as well as butyrylcholinesterase in a dose-dependent manner with IC50 values of 20.1 ± 1.1 μM and 85.2 ± 3.2 μM, respectively. (+)-Canadine, with an IC50 value of 12.4 ± 0.9 μM, was the most potent inhibitor of acetylcholinesterase, whilst (±)-corycavidine and (+)-bulbocapnine were effective inhibitors of butyrylcholinesterase with IC50 values of 46.2 ± 2.4 uM and 67.0 ± 2.1 μM, respectively. The other isolated alkaloids were considered inactive (IC50 > 100 μM).

scholarly journals THE EFFECT OF POLY-L-LYSINE ON THE UPTAKE OF REOVIRUS DOUBLE-STRANDED RNA IN MACROPHAGES IN VITRO

1973 ◽  
Vol 57 (2) ◽  
pp. 484-498 ◽  
Author(s):  
Rolf Seljelid ◽  
Samuel C. Silverstein ◽  
Zanvil A. Cohn
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Nucleic Acids ◽  
Acid Hydrolases ◽  
Cell Compartment ◽  
Double Stranded Rna ◽  
Secondary Lysosomes ◽  
Toxic Concentrations ◽  
Vacuolar System

The effect of polycations on cultured mouse peitoneal macrophages has been examined. Polycations, at concentrations greater than 5 µg/ml, are toxic for macrophages) as measured by failure of the cells to exclude vital dyes. At toxic concentrations polycations bind in large amounts to nuclei and endoplasmic reticulum, while at nontoxic levels polycations bind selectively to the cell surface. Nontoxic concentrations of polycations stimulate binding of reovirus double-stranded (ds) RNA to the macrophages by forming polycation-dsRNA complexes either in the medium or at the cell surface. These complexes enter the cell in endocytic vacuoles and are concentrated in secondary lysosomes. Despite exposure to the acid hydrolases within this cell compartment, the dsRNA and the polycation (poly-L-lysine) are conserved in a macromolecular form within the vacuolar system. The mechanism(s) by which the uptake of infectious nucleic acids and the induction of interferon by dsRNA are stimulated by polycations are discussed.

Influence of poly(I:C) variability on thermoregulation, immune responses and pregnancy outcomes in mouse models of maternal immune activation

2019 ◽  
Vol 80 ◽  
pp. 406-418 ◽  
Author(s):  
Flavia S. Mueller ◽  
Juliet Richetto ◽  
Lindsay N. Hayes ◽  
Alice Zambon ◽  
Daniela D. Pollak ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mouse Models ◽  
Immune Activation ◽  
Pregnancy Outcomes ◽  
Poly I:C ◽  
Maternal Immune Activation
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