scholarly journals Adipose type I interferon signalling protects against metabolic dysfunction

2017 ◽  
Vol 66 (1) ◽  
pp. S609
Author(s):  
T. Adolph ◽  
V. Wieser ◽  
C. Grander ◽  
F. Grabherr ◽  
B. Enrich ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Interferon Signalling

scholarly journals Stat2 loss disrupts damage signalling and is protective in acute pancreatitis

2019 ◽  
Author(s):  
Helen Heath ◽  
Gary Britton ◽  
Hiromi Kudo ◽  
George Renney ◽  
Malcolm Ward ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Pancreatitis ◽  
Type I Interferon ◽  
Pancreatic Tissue ◽  
Sterile Inflammation ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Label Free ◽  
Bone Marrow Chimera ◽  
Interferon Signalling

ABSTRACTSeverity of sterile inflammation, as seen in acute pancreatitis, is determined by damage-sensing receptors, signalling cascades and cytokine production. Stat2 is a type I interferon signalling mediator that also has interferon-independent roles in murine lipopolysaccharide-induced NF-κB-mediated sepsis. However its role in sterile inflammation is unknown. We hypothesised that Stat2 determines severity of non-infective inflammation in the pancreas.Wild type (WT) and Stat2−/− mice were injected intraperitoneally with cerulein or L-arginine. Specific cytokine-blocking antibodies were used in some experiments. Pancreata and blood were harvested 1h and 24h after the final dose of cerulein and up to 96h post L-arginine. Whole-tissue phosphoproteomic changes were assessed using label-free mass spectrometry. Tissue-specific Stat2 effects were studied in WT/Stat2−/− bone-marrow chimera and using Cre-lox recombination to delete Stat2 in pancreatic and duodenal homeobox 1(Pdx1)-expressing cells.Stat2−/− mice were protected from cerulein- and L-arginine-induced pancreatitis. Protection was independent of type I interferon signalling. Stat2−/− mice had lower cytokine levels including TNFα and IL-10 and reduced NF-kB nuclear localisation in pancreatic tissue compared to WT. Inhibition of TNFα improved (inhibition of IL-10 worsened) cerulein-induced pancreatitis in WT but not Stat2−/− mice. Phosphoproteomics showed down-regulation of mitogen-activated protein kinase (MAPK) mediators but accumulation of Ser412-phosphorylated Tak1. Stat2 deletion in Pdx1-expressing acinar cells (Stat2flox/Pdx1-cre) reduced pancreatic TNFα expression, but not histological injury or serum amylase. WT/Stat2−/− bone-marrow chimera were protected from pancreatitis irrespective of host or recipient genotype.Stat2 loss results in disrupted signalling in pancreatitis, upstream of NF-κB in non-acinar and/or bone marrow derived cells.

scholarly journals Type I interferon potentiates metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2020 ◽  
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Polymerase Gamma

AbstractMitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune crosstalk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA (mtDNA) instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces healthspan, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increases oxidative stress, enhances pro-inflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyper-inflammatory phenotypes by restoring Nrf2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related diseases and aging.

AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling

2018 ◽  
Vol 3 (3) ◽  
pp. 302-309 ◽  
Author(s):  
Jian Chen ◽  
Yi-feng Yang ◽  
Yu Yang ◽  
Peng Zou ◽  
Jun Chen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Type I Interferon ◽  
Type I ◽  
Zika Virus Infection ◽  
Interferon Signalling

scholarly journals Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2450
Author(s):  
Aneta Gandalovičová ◽  
Anna-Marie Šůchová ◽  
Vladimír Čermák ◽  
Ladislav Merta ◽  
Daniel Rösel ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Type I Interferon ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Melanoma Cells ◽  
Interferon Response ◽  
Type I ◽  
Expression Of Genes ◽  
Interferon Signalling ◽  
Inflammatory Signalling

The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal–amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.

scholarly journals Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition of Type I Interferon Signalling

Viruses ◽  
2017 ◽  
Vol 9 (11) ◽  
pp. 326 ◽  
Author(s):  
Yin Setoh ◽  
Parthiban Periasamy ◽  
Nias Peng ◽  
Alberto Amarilla ◽  
Andrii Slonchak ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Type I Interferon ◽  
Helicase Domain ◽  
Type I ◽  
West Nile ◽  
Ns3 Protein ◽  
Interferon Signalling

Type I interferon signalling is not required for the induction of endotoxin tolerance

Cytokine ◽  
2017 ◽  
Vol 95 ◽  
pp. 7-11 ◽  
Author(s):  
Yalda Karimi ◽  
Sophie M. Poznanski ◽  
Fatemeh Vahedi ◽  
Branson Chen ◽  
Marianne V. Chew ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Endotoxin Tolerance ◽  
Type I ◽  
Interferon Signalling

scholarly journals The X proteins of bornaviruses interfere with type I interferon signalling

2013 ◽  
Vol 94 (2) ◽  
pp. 263-269 ◽  
Author(s):  
Jonas Johansson Wensman ◽  
Muhammad Munir ◽  
Srinivas Thaduri ◽  
Katarina Hörnaeus ◽  
Muhammad Rizwan ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Rna Virus ◽  
Luciferase Reporter ◽  
Type I ◽  
Type I Ifn ◽  
X Protein ◽  
Wide Range ◽  
Reporter Assays ◽  
Interferon Signalling

Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus causing persistent infection and progressive neurological disorders in a wide range of warm-blooded animals. The role of the small non-structural X protein in viral pathogenesis is not completely understood. Here we investigated whether the X protein of BDV and avian bornavirus (ABV) interferes with the type I interferon (IFN) system, similar to other non-structural proteins of negative-stranded RNA viruses. In luciferase reporter assays, we found that the X protein of various bornaviruses interfered with the type I IFN system at all checkpoints investigated, in contrast to previously reported findings, resulting in reduced type I IFN secretion.

scholarly journals Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice

2021 ◽  
Vol 7 (22) ◽  
pp. eabe7548
Author(s):  
Yuanjiu Lei ◽  
Camila Guerra Martinez ◽  
Sylvia Torres-Odio ◽  
Samantha L. Bell ◽  
Christine E. Birdwell ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Aerobic Glycolysis ◽  
Accelerated Aging ◽  
Innate Immune ◽  
Related Factor ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Elevated Type

Mitochondrial dysfunction is a key driver of inflammatory responses in human disease. However, it remains unclear whether alterations in mitochondria-innate immune cross-talk contribute to the pathobiology of mitochondrial disorders and aging. Using the polymerase gamma (POLG) mutator model of mitochondrial DNA instability, we report that aberrant activation of the type I interferon (IFN-I) innate immune axis potentiates immunometabolic dysfunction, reduces health span, and accelerates aging in mutator mice. Mechanistically, elevated IFN-I signaling suppresses activation of nuclear factor erythroid 2–related factor 2 (NRF2), which increases oxidative stress, enhances proinflammatory cytokine responses, and accelerates metabolic dysfunction. Ablation of IFN-I signaling attenuates hyperinflammatory phenotypes by restoring NRF2 activity and reducing aerobic glycolysis, which combine to lessen cardiovascular and myeloid dysfunction in aged mutator mice. These findings further advance our knowledge of how mitochondrial dysfunction shapes innate immune responses and provide a framework for understanding mitochondria-driven immunopathology in POLG-related disorders and aging.

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