Interferon-α therapy does not modulate hepatic expression of classical type I interferon inducible genes

2008 ◽  
Vol 80 (11) ◽  
pp. 1912-1918 ◽  
Author(s):  
Volker Meier ◽  
Sabine Mihm ◽  
Giuliano Ramadori
Keyword(s):  
Type I Interferon ◽  
Classical Type ◽  
Interferon Α ◽  
Type I ◽  
Hepatic Expression ◽  
Inducible Genes

scholarly journals The Abstruse Side of Type I Interferon Immunotherapy for COVID-19 Cases with Comorbidities

2021 ◽  
Vol 1 (1) ◽  
pp. 49-59
Author(s):  
Selvakumar Subbian
Keyword(s):  
Infectious Diseases ◽  
Disease Severity ◽  
Type I Interferon ◽  
Host Factors ◽  
Type I ◽  
The Novel ◽  
Inflammatory Drugs ◽  
Precautionary Measures ◽  
Inducible Genes

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19.

scholarly journals Vaccinia Virus B18R Gene Encodes a Type I Interferon-binding Protein That Blocks Interferon α Transmembrane Signaling

1995 ◽  
Vol 270 (27) ◽  
pp. 15974-15978 ◽  
Author(s):  
Oscar R. Colamonici ◽  
Paul Domanski ◽  
Sharon M. Sweitzer ◽  
Andrew Larner ◽  
R. Mark L. Buller
Keyword(s):  
Vaccinia Virus ◽  
Type I Interferon ◽  
Binding Protein ◽  
Interferon Α ◽  
Type I ◽  
Transmembrane Signaling

miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5885-5894 ◽  
Author(s):  
Haibo Zhou ◽  
Xinfang Huang ◽  
Huijuan Cui ◽  
Xiaobing Luo ◽  
Yuanjia Tang ◽  
...  
Keyword(s):  
Gene Expression Regulation ◽  
Type I Interferon ◽  
Early Stage ◽  
Plasmacytoid Dendritic Cell ◽  
Interferon Α ◽  
Type I ◽  
Interferon Production ◽  
Novel Mirna ◽  
Star Form ◽  
Single Precursor

Abstract The recent discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation, affecting the immune system. Here, we identify their roles in regulating human plasmacytoid dendritic cell (PDC) activation. miRNA profiling showed the significantly differential expression of 19 miRNAs in PDCs after Toll-like receptor 7 (TLR7) stimulation, among which miR-155* and miR-155 were the most highly induced. Although they were processed from a single precursor and were both induced by TLR7 through the c-Jun N-terminal kinase pathway, miR-155* and miR-155 had opposite effects on the regulation of type I interferon production by PDC. Further study indicated that miR-155* augmented interferon-α/β expression by suppressing IRAKM, whereas miR-155 inhibited their expression by targeting TAB2. Kinetic analysis of miR-155* and miR-155 induction revealed that miR-155* was mainly induced in the early stage of stimulation, and that miR-155 was mainly induced in the later stage, suggesting their cooperative involvement in PDC activation. Finally, we demonstrated that miR-155* and miR-155 were inversely regulated by autocrine/paracrine type I interferon and TLR7-activated KHSRP at the posttranscriptional level, which led to their different dynamic induction by TLR7. Thus, our study identified and validated novel miRNA-protein networks involved in regulating PDC activation.

scholarly journals B7–H3 regulates osteoclast differentiation via type I interferon-dependent IDO induction

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Younseo Oh ◽  
Robin Park ◽  
So Yeon Kim ◽  
Sung-ho Park ◽  
Sungsin Jo ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Osteoblast Differentiation ◽  
Type I Interferon ◽  
Osteoclast Differentiation ◽  
Regulatory Function ◽  
Type I ◽  
Type I Ifn ◽  
B7 Family ◽  
Human Osteoclast ◽  
Inducible Genes

AbstractWhile their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7–H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7–H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7–H3 is highly expressed in mature osteoclasts and that B7–H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7–H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7–H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7–H3, inhibition of B7–H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7–H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN–IDO signaling as its downstream mechanism.

scholarly journals Plasmacytoid Dendritic Cells Mediate Myocardial Ischemia/Reperfusion Injury by Secreting Type I Interferons

2021 ◽  
Author(s):  
Lina Lai ◽  
Aimee Zhang ◽  
Boris Yang ◽  
Eric J. Charles ◽  
Irving L. Kron ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Cyclic Gmp ◽  
Type I Interferon ◽  
Ischemia Reperfusion ◽  
Interferon Α ◽  
Type I ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background We previously demonstrated that ischemically injured cardiomyocytes release cell‐free DNA and HMGB1 (high mobility group box 1 protein) into circulation during reperfusion, activating proinflammatory responses and ultimately exacerbating reperfusion injury. We hypothesize that cell‐free DNA and HMGB1 mediate myocardial ischemia‐reperfusion injury by stimulating plasmacytoid dendritic cells (pDCs) to secrete type I interferon (IFN‐I). Methods and Results C57BL/6 and interferon alpha receptor‐1 knockout mice underwent 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion (40′/60′ IR) before infarct size was evaluated by 2,3,5‐Triphenyltetrazolium chloride–Blue staining. Cardiac perfusate was acquired in ischemic hearts without reperfusion by antegrade perfusion of the isolated heart. Flow cytometry in pDC‐depleted mice treated with multiple doses of plasmacytoid dendritic cell antigen‐1 antibody via intraperitoneal injection demonstrated plasmacytoid dendritic cell antigen‐1 antibody treatment had no effect on conventional splenic dendritic cells but significantly reduced splenic pDCs by 60%. pDC‐depleted mice had significantly smaller infarct size and decreased plasma interferon‐α and interferon‐β compared with control. Blockade of the type I interferon signaling pathway with cyclic GMP‐AMP synthase inhibitor, stimulator of interferon genes antibody, or interferon regulatory factor 3 antibody upon reperfusion similarly significantly attenuated infarct size by 45%. Plasma levels of interferon‐α and interferon‐β were significantly reduced in cyclic GMP‐AMP synthase inhibitor‐treated mice. Infarct size was significantly reduced by >30% in type I interferon receptor monoclonal antibody–treated mice and interferon alpha receptor‐1 knockout mice. In splenocyte culture, 40′/0′ cardiac perfusate treatment stimulated interferon‐α and interferon‐β production; however, this effect disappeared in the presence of cyclic GMP‐AMP synthase inhibitor. Conclusions Type I interferon production is stimulated following myocardial ischemia by cardiogenic cell‐free DNA/HMGB1 in a pDC‐dependent manner, and subsequently activates type I interferon receptors to exacerbate reperfusion injury. These results identify new potential therapeutic targets to attenuate myocardial ischemia‐reperfusion injury.

scholarly journals Suppressor of Cytokine Signaling (SOCS) 1 Inhibits Type I Interferon (IFN) Signaling via the Interferon α Receptor (IFNAR1)-associated Tyrosine Kinase Tyk2

2011 ◽  
Vol 286 (39) ◽  
pp. 33811-33818 ◽  
Author(s):  
Rebecca A. R. Piganis ◽  
Nicole A. De Weerd ◽  
Jodee A. Gould ◽  
Christian W. Schindler ◽  
Ashley Mansell ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Type I Interferon ◽  
Cytokine Signaling ◽  
Interferon Α ◽  
Type I ◽  
Suppressor Of Cytokine Signaling
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