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Article ; Online: The Superiority of Sucrose Cushion Centrifugation to Ultrafiltration and PEGylation in Generating High-Titer Lentivirus Particles and Transducing Stem Cells with Enhanced Efficiency.

Boroujeni, Mahdi Eskandarian / Gardaneh, Mossa

2018 Volume 60, Issue 3, Page(s) 185–193

Abstract: Viral gene delivery is hailed as a great milestone in gene-based therapeutic approaches. The human immunodeficiency virus-derived lentiviral vectors (LVs) are advantageous in infecting both dividing and non-dividing cells leading to continuous expression ...

Abstract	Viral gene delivery is hailed as a great milestone in gene-based therapeutic approaches. The human immunodeficiency virus-derived lentiviral vectors (LVs) are advantageous in infecting both dividing and non-dividing cells leading to continuous expression of transgenes. A variety of protocols are available for concentration of LVs. We primarily generated our internal ribosome entry site (IRES)-based LVs. Virus titration and transduction efficiency were compared between various strategies that included sucrose cushion centrifugation (SCC), protein column ultrafiltration and polyethylene glycol precipitation. Among these approaches, SCC resulted in concentration of high-titer EGFP-expressing lentivirus (1.4 ± 0.3 × 10
MeSH term(s)	Animals ; Cell Line ; Centrifugation/methods ; Genetic Vectors/metabolism ; Humans ; Lentivirus/metabolism ; Mice ; Polyethylene Glycols/chemistry ; Recombination, Genetic/genetics ; Stem Cells/metabolism ; Sucrose/chemistry ; Transduction, Genetic ; Transgenes ; Ultrafiltration/methods ; Viral Load
Chemical Substances	Polyethylene Glycols (30IQX730WE) ; Sucrose (57-50-1)
Language	English
Publishing date	2018-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1193057-3
ISSN	1559-0305 ; 1073-6085
ISSN (online)	1559-0305
ISSN	1073-6085
DOI	10.1007/s12033-017-0044-5
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Zs.A 4031: Show issues

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Article ; Online: Time-dependent recruitment of GAF, ISGF3 and IRF1 complexes shapes IFNα and IFNγ-activated transcriptional responses and explains mechanistic and functional overlap.

Sekrecka, Agata / Kluzek, Katarzyna / Sekrecki, Michal / Boroujeni, Mahdi Eskandarian / Hassani, Sanaz / Yamauchi, Shota / Sada, Kiyonao / Wesoly, Joanna / Bluyssen, Hans A R

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 7, Page(s) 187

Abstract: To understand in detail the transcriptional and functional overlap of IFN-I- and IFN-II-activated responses, we used an integrative RNAseq-ChIPseq approach in Huh7.5 cells and characterized the genome-wide role of pSTAT1, pSTAT2, IRF9 and IRF1 in time- ... ...

Abstract	To understand in detail the transcriptional and functional overlap of IFN-I- and IFN-II-activated responses, we used an integrative RNAseq-ChIPseq approach in Huh7.5 cells and characterized the genome-wide role of pSTAT1, pSTAT2, IRF9 and IRF1 in time-dependent ISG expression. For the first time, our results provide detailed insight in the timely steps of IFNα- and IFNγ-induced transcription, in which pSTAT1- and pSTAT2-containing ISGF3 and GAF-like complexes and IRF1 are recruited to individual or combined ISRE and GAS composite sites in a phosphorylation- and time-dependent manner. Interestingly, composite genes displayed a more heterogeneous expression pattern, as compared to GAS (early) and ISRE genes (late), with the time- and phosphorylation-dependent recruitment of GAF, ISGF3 and IRF1 after IFNα stimulation and GAF and IRF1 after IFNγ. Moreover, functional composite genes shared features of GAS and ISRE genes through transcription factor co-binding to closely located sites, and were able to sustain IFN responsiveness in STAT1-, STAT2-, IRF9-, IRF1- and IRF9/IRF1-mutant Huh7.5 cells compared to Wt cells. Thus, the ISRE + GAS composite site acted as a molecular switch, depending on the timely available components and transcription factor complexes. Consequently, STAT1, STAT2 and IRF9 were identified as functional composite genes that are part of a positive feedback loop controlling long-term IFNα and IFNγ responses. More important, in the absence of any one of the components, the positive feedback regulation of the ISGF3 and GAF components appeared to be preserved. Together, these findings provide further insight in the existence of a novel ISRE + GAS composite-dependent intracellular amplifier circuit prolonging ISG expression and controlling cellular responsiveness to different types of IFNs and subsequent antiviral activity. It also offers an explanation for the existing molecular and functional overlap between IFN-I- and IFN-II-activated ISG expression.
MeSH term(s)	Interferon-alpha/pharmacology ; Interferon-alpha/genetics ; Interferon-gamma/pharmacology ; Interferon-gamma/metabolism ; Gene Expression Regulation ; Antiviral Agents ; Interferon Type I/metabolism ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; STAT2 Transcription Factor/genetics ; STAT2 Transcription Factor/metabolism
Chemical Substances	Interferon-alpha ; Interferon-gamma (82115-62-6) ; Antiviral Agents ; Interferon Type I ; STAT1 Transcription Factor ; STAT2 Transcription Factor
Language	English
Publishing date	2023-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-04830-8
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Article: Umbilical cord: an unlimited source of cells differentiable towards dopaminergic neurons.

Boroujeni, Mahdi Eskandarian / Gardaneh, Mossa

Neural regeneration research

2017 Volume 12, Issue 7, Page(s) 1186–1192

Abstract: Cell replacement therapy utilizing mesenchymal stem cells as its main resource holds great promise for ultimate treatment of human neurological disorders. Parkinson's disease (PD) is a common, chronic neurodegenerative disorder hallmarked by localized ... ...

Abstract	Cell replacement therapy utilizing mesenchymal stem cells as its main resource holds great promise for ultimate treatment of human neurological disorders. Parkinson's disease (PD) is a common, chronic neurodegenerative disorder hallmarked by localized degeneration of a specific set of dopaminergic neurons within a midbrain sub-region. The specific cell type and confined location of degenerating neurons make cell replacement therapy ideal for PD treatment since it mainly requires replenishment of lost dopaminergic neurons with fresh and functional ones. Endogenous as well as exogenous cell sources have been identified as candidate targets for cell replacement therapy in PD. In this review, umbilical cord mesenchymal stem cells (UCMSCs) are discussed as they provide an inexpensive unlimited reservoir differentiable towards functional dopaminergic neurons that potentially lead to long-lasting behavioral recovery in PD patients. We also present miRNAs-mediated neuronal differentiation of UCMSCs. The UCMSCs bear a number of outstanding characteristics including their non-tumorigenic, low-immunogenic properties that make them ideal for cell replacement therapy purposes. Nevertheless, more investigations as well as controlled clinical trials are required to thoroughly confirm the efficacy of UCMSCs for therapeutic medical-grade applications in PD.
Language	English
Publishing date	2017-08-29
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.211201
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Article ; Online: Anti-inflammatory effect of green photobiomodulation in human adipose-derived mesenchymal stem cells.

Tamimi, Reyhaneh / Mahmoodi, Nadia Malek / Samadikhah, Hamid Reza / Tackallou, Saeed Hesami / Benisi, Soheila Zamanlui / Boroujeni, Mahdi Eskandarian

Lasers in medical science

2022 Volume 37, Issue 9, Page(s) 3693–3703

Abstract: Photo biomodulation (PBM) as a non-invasive and safe treatment has been demonstrated the anti-inflammatory potential in a variety of cell types, including stem cells. However, further investigations using different laser parameters combined with more ... ...

Abstract	Photo biomodulation (PBM) as a non-invasive and safe treatment has been demonstrated the anti-inflammatory potential in a variety of cell types, including stem cells. However, further investigations using different laser parameters combined with more accurate methods such as quantitative measurement of inflammatory gene expression at the mRNA level are still necessary. The aim of this study was to evaluate the effect of 532 nm green laser on cell proliferation as well as expression of inflammatory genes in human adipose-derived mesenchymal stem cells (hADMSCs) using RNA sequencing (RNA-seq) technique and confirmatory RT-PCR. hADMSCs were cultured in DMEM low glocuse medium with 10% fetal bovine serum until the fourth passage. Cultured cells were divided in two groups: control group (no laser irradiation) and laser group, irradiated with 532 nm laser at 44 m J/cm
MeSH term(s)	Humans ; Mesenchymal Stem Cells ; Stem Cells ; Cell Proliferation/genetics ; Cell Survival ; Cell Line
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	632808-8
ISSN	1435-604X ; 0268-8921
ISSN (online)	1435-604X
ISSN	0268-8921
DOI	10.1007/s10103-022-03654-5
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Zs.A 2148: Show issues

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Article ; Online: Complementation of dopaminergic signaling by Pitx3-GDNF synergy induces dopamine secretion by multipotent Ntera2 cells.

Eskandarian Boroujeni, Mahdi / Aliaghaei, Abbas / Maghsoudi, Nader / Gardaneh, Mossa

Journal of cellular biochemistry

2019 Volume 121, Issue 1, Page(s) 200–212

Abstract: Human teratocarcinoma cell line Ntera2 (NT2) expresses dopamine signals and has shown its safe profile for clinical applications. Attempts to restore complete dopaminergic (DAergic) phenotype enabling these cells to secrete dopamine have not been fully ... ...

Abstract	Human teratocarcinoma cell line Ntera2 (NT2) expresses dopamine signals and has shown its safe profile for clinical applications. Attempts to restore complete dopaminergic (DAergic) phenotype enabling these cells to secrete dopamine have not been fully successful so far. We applied a blend of gene transfer techniques and a defined medium to convert NT2 cells to fully DAergic. The cells were primarily engineered to overexpress the Pitx3 gene product and then cultured in a growth medium supplemented with knockout serum and retinoic acid to form embroid bodies (EBs). Trypsinization of EB colonies produced single cells ready for differentiation. Neuronal/DAergic induction was promoted by applying conditioned medium taken from engineered human astrocytomas over-secreting glial cell-derived neurotrophic factor (GDNF). Immunocytochemistry, reverse-transcription and real-time polymerase chain reaction analyses confirmed significantly induced expression of molecules involved in dopamine signaling and metabolism including tyrosine hydroxylase, Nurr1, dopamine transporter, and aromatic acid decarboxylase. High-performance liquid chromatography analysis indicated release of dopamine only from a class of fully differentiated cells expressing Pitx3 and exposed to GDNF. In addition, Pitx3 and GDNF additively promoted in vitro neuroprotection against Parkinsonian toxin. One month after transplantation to the striatum of 6-OHDA-leasioned rats, differentiated NT2 cells survived and induced significant increase in striatal volume. Besides, cell implantation improved motor coordination in Parkinson's disease (PD) rat models. Our findings highlight the importance of Pitx3-GDNF interplay in dopamine signaling and indicate that our strategy might be useful for the restoration of DAergic fate of NT2 cells to make them clinically applicable toward cell replacement therapy of PD.
MeSH term(s)	Animals ; Astrocytoma/metabolism ; Behavior, Animal ; Cell Differentiation ; Cell Line, Tumor ; Culture Media, Conditioned ; Dopamine/metabolism ; Dopaminergic Neurons/metabolism ; Gene Transfer Techniques ; Genetic Complementation Test ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; HEK293 Cells ; Homeodomain Proteins/metabolism ; Humans ; Oxidopamine/pharmacology ; Parkinson Disease/metabolism ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/metabolism ; Tretinoin/metabolism
Chemical Substances	Culture Media, Conditioned ; Glial Cell Line-Derived Neurotrophic Factor ; Homeodomain Proteins ; Transcription Factors ; homeobox protein PITX3 ; Tretinoin (5688UTC01R) ; Oxidopamine (8HW4YBZ748) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2019-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.29109
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Zs.A 1114: Show issues

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Article ; Online: Functional and structural alternations in the choroid plexus upon methamphetamine exposure.

Hassani Moghaddam, Meysam / Eskandarian Boroujeni, Mahdi / Vakili, Kimia / Fathi, Mobina / Abdollahifar, Mohammad-Amin / Eskandari, Neda / Esmaeilpour, Tahereh / Aliaghaei, Abbas

Neuroscience letters

2021 Volume 764, Page(s) 136246

Abstract: Choroid plexus (CP) is the principal source of cerebrospinal fluid. CP can produce and release a wide range of materials including growth factors, neurotrophic factors, etc. all of which play an important role in the maintenance and proper functioning of ...

Abstract	Choroid plexus (CP) is the principal source of cerebrospinal fluid. CP can produce and release a wide range of materials including growth factors, neurotrophic factors, etc. all of which play an important role in the maintenance and proper functioning of the brain. Methamphetamine (METH) is a CNS neurostimulant that causes brain dysfunction. Herein, we investigated the potential effects of METH exposure on CP structure and function. Stereological analysis revealed a significant alteration in CP volume, epithelial cells and capillary number upon METH treatment. Electron microscopy exhibited changes in ultrastructure. Moreover, the upregulation of neurotrophic factors such as BDNF and VEGF as well as autophagy and apoptosis gene following METH administration were observed. We also identified several signaling cascades related to autophagy. In conclusion, gene expression changes coupled with structural alterations of the CP in response to METH suggested METH-induced autophagy in CP.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Autophagy/drug effects ; Autophagy/genetics ; Brain-Derived Neurotrophic Factor/analysis ; Brain-Derived Neurotrophic Factor/metabolism ; Caspase 3/analysis ; Caspase 3/metabolism ; Central Nervous System Stimulants/administration & dosage ; Central Nervous System Stimulants/toxicity ; Choroid Plexus/cytology ; Choroid Plexus/drug effects ; Choroid Plexus/pathology ; Epithelial Cells/drug effects ; Epithelial Cells/pathology ; Epithelial Cells/ultrastructure ; Injections, Intraperitoneal ; Male ; Methamphetamine/administration & dosage ; Methamphetamine/toxicity ; Microscopy, Electron, Transmission ; Rats ; Up-Regulation/drug effects ; Vascular Endothelial Growth Factor A/analysis ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Bdnf protein, rat ; Brain-Derived Neurotrophic Factor ; Central Nervous System Stimulants ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, rat ; Methamphetamine (44RAL3456C) ; Casp3 protein, rat (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2021-09-14
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2021.136246
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Article: Anti-inflammatory and antioxidative effects of elderberry diet in the rat model of seizure: a behavioral and histological investigation on the hippocampus.

Bayat, Amir-Hossein / Eskandari, Neda / Sani, Mojtaba / Fotouhi, Farid / Shenasandeh, Zahra / Saeidikhoo, Sara / Rohani, Razieh / Sabbagh Alvani, Mohammadamin / Mafi Balani, Mohammadreza / Eskandarian Boroujeni, Mahdi / Abdollahifar, Mohammad-Amin / Tajari, Faezeh / Aliaghaei, Abbas / Hassani Moghaddam, Meysam

Toxicology research

2023 Volume 12, Issue 5, Page(s) 783–795

Abstract: The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the ... ...

Abstract	The present study was designed to evaluate whether elderberry (EB) effectively reduces inflammation and oxidative stress in hippocampal cells to modify seizure damage. Seizure was induced in rats by the injection of pentylenetetrazol (PTZ). In the Seizure + EB group, EB powder was added to the rats' routine diet for eight consecutive weeks. The study included several behavioral tests, immunohistopathology, Voronoi tessellation (to estimate the spatial distribution of cells in the hippocampus), and Sholl analysis. The results in the Seizure + EB group showed an improvement in the behavioral aspects of the study, a reduction in astrogliosis, astrocyte process length, number of branches, and intersections distal to the soma in the hippocampus of rats compared to controls. Further analysis showed that EB diet increased nuclear factor-like 2 expression and decreased caspase-3 expression in the hippocampus in the Seizure + EB group. In addition, EB protected hippocampal pyramidal neurons from PTZ toxicity and improved the spatial distribution of hippocampal neurons in the pyramidal layer and dentate gyrus. The results of the present study suggest that EB can be considered a potent modifier of astrocyte reactivation and inflammatory responses.
Language	English
Publishing date	2023-08-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2684701-2
ISSN	2045-4538 ; 2045-452X
ISSN (online)	2045-4538
ISSN	2045-452X
DOI	10.1093/toxres/tfad070
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Article ; Online: COVID-19 causes neuronal degeneration and reduces neurogenesis in human hippocampus.

Bayat, Amir-Hossein / Azimi, Helia / Hassani Moghaddam, Meysam / Ebrahimi, Vahid / Fathi, Mobina / Vakili, Kimia / Mahmoudiasl, Gholam-Reza / Forouzesh, Mahdi / Boroujeni, Mahdi Eskandarian / Nariman, Zahra / Abbaszadeh, Hojjat-Allah / Aryan, Arefeh / Aliaghaei, Abbas / Abdollahifar, Mohammad-Amin

Apoptosis : an international journal on programmed cell death

2022 Volume 27, Issue 11-12, Page(s) 852–868

Abstract: Recent investigations of COVID-19 have largely focused on the effects of this novel virus on the vital organs in order to efficiently assist individuals who have recovered from the disease. In the present study we used hippocampal tissue samples ... ...

Abstract	Recent investigations of COVID-19 have largely focused on the effects of this novel virus on the vital organs in order to efficiently assist individuals who have recovered from the disease. In the present study we used hippocampal tissue samples extracted from people who died after COVID-19. Utilizing histological techniques to analyze glial and neuronal cells we illuminated a massive degeneration of neuronal cells and changes in glial cells morphology in hippocampal samples. The results showed that in hippocampus of the studied brains there were morphological changes in pyramidal cells, an increase in apoptosis, a drop in neurogenesis, and change in spatial distribution of neurons in the pyramidal and granular layer. It was also demonstrated that COVID-19 alter the morphological characteristics and distribution of astrocyte and microglia cells. While the exact mechanism(s) by which the virus causes neuronal loss and morphology in the central nervous system (CNS) remains to be determined, it is necessary to monitor the effect of SARS-CoV-2 infection on CNS compartments like the hippocampus in future investigations. As a result of what happened in the hippocampus secondary to COVID-19, memory impairment may be a long-term neurological complication which can be a predisposing factor for neurodegenerative disorders through neuroinflammation and oxidative stress mechanisms.
MeSH term(s)	Humans ; COVID-19 ; Apoptosis ; SARS-CoV-2 ; Neurogenesis/physiology ; Hippocampus ; Causality
Language	English
Publishing date	2022-07-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1452360-7
ISSN	1573-675X ; 1360-8185
ISSN (online)	1573-675X
ISSN	1360-8185
DOI	10.1007/s10495-022-01754-9
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Zs.A 5178: Show issues

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Article ; Online: Differential gene expression and stereological analyses of the cerebellum following methamphetamine exposure.

Eskandarian Boroujeni, Mahdi / Peirouvi, Tahmineh / Shaerzadeh, Fatemeh / Ahmadiani, Abolhasan / Abdollahifar, Mohammad Amin / Aliaghaei, Abbas

Addiction biology

2019 Volume 25, Issue 1, Page(s) e12707

Abstract: Methamphetamine (METH) is a highly addictive psychostimulant that profoundly aimed at monoaminergic systems in the brain. Despite the leading role of cerebellum in sensorimotor control as well as augmented locomotor activity under the influence of METH, ... ...

Abstract	Methamphetamine (METH) is a highly addictive psychostimulant that profoundly aimed at monoaminergic systems in the brain. Despite the leading role of cerebellum in sensorimotor control as well as augmented locomotor activity under the influence of METH, there are few studies examining the effect of METH administration on gene expression profiling and structural consequences in the cerebellar region. Thus, we sought to explore the effects of METH on the cerebellum, from gene expression changes to structural alterations. In this respect, we investigated genome-wide mRNA expression using high throughput RNA-seq technology and confirmatory quantitative real-time PCR, accompanied by stereological analysis of cerebellar layers along with identification of reactive astrogliosis by glial fibrillary acidic protein and behavioral assessment following METH exposure. According to our RNA-seq data, 473 unique differentially expressed genes (DEG) were detected upon METH injections in which a large number of these genes engage basically in biological regulations and metabolic processes, chiefly located in nucleus and membrane. In addition, pathway analysis of METH-induced DEG revealed several enriched signaling cascades related largely to immune response, neurotransmission, cell growth, and death. Further, METH induced a significant reduction in volumes of cerebellar layers (molecular, granular, and Purkinje) and a decrease in the white matter volume along with a rise in astrogliosis as well as increased locomotor activity. In conclusion, considering gene expression changes combined with structural alterations of the cerebellum in response to METH, these data suggest METH-induced neurotoxicity in the cerebellar region.
MeSH term(s)	Amphetamine-Related Disorders/physiopathology ; Animals ; Central Nervous System Stimulants/pharmacology ; Cerebellum/drug effects ; Cerebellum/physiopathology ; Disease Models, Animal ; Gene Expression/drug effects ; Male ; Methamphetamine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects
Chemical Substances	Central Nervous System Stimulants ; Methamphetamine (44RAL3456C)
Language	English
Publishing date	2019-02-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1324314-7
ISSN	1369-1600 ; 1355-6215
ISSN (online)	1369-1600
ISSN	1355-6215
DOI	10.1111/adb.12707
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Article ; Online: Dysregulated Interferon Response and Immune Hyperactivation in Severe COVID-19: Targeting STATs as a Novel Therapeutic Strategy.

Eskandarian Boroujeni, Mahdi / Sekrecka, Agata / Antonczyk, Aleksandra / Hassani, Sanaz / Sekrecki, Michal / Nowicka, Hanna / Lopacinska, Natalia / Olya, Arta / Kluzek, Katarzyna / Wesoly, Joanna / Bluyssen, Hans A R

Frontiers in immunology

2022 Volume 13, Page(s) 888897

Abstract: A disease outbreak in December 2019, caused by a novel coronavirus SARS-CoV-2, was named COVID-19. SARS-CoV-2 infects cells from the upper and lower respiratory tract system and is transmitted by inhalation or contact with infected droplets. Common ... ...

Abstract	A disease outbreak in December 2019, caused by a novel coronavirus SARS-CoV-2, was named COVID-19. SARS-CoV-2 infects cells from the upper and lower respiratory tract system and is transmitted by inhalation or contact with infected droplets. Common clinical symptoms include fatigue, fever, and cough, but also shortness of breath and lung abnormalities. Still, some 5% of SARS-CoV-2 infections progress to severe pneumonia and acute respiratory distress syndrome (ARDS), with pulmonary edema, acute kidney injury, and/or multiple organ failure as important consequences, which can lead to death. The innate immune system recognizes viral RNAs and triggers the expression of interferons (IFN). IFNs activate anti-viral effectors and components of the adaptive immune system by activating members of the STAT and IRF families that induce the expression of IFN-stimulated genes (ISG)s. Among other coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, common strategies have been identified to antagonize IFN signaling. This typically coincides with hyperactive inflammatory host responses known as the "cytokine storm" that mediate severe lung damage. Likewise, SARS-CoV-2 infection combines a dysregulated IFN response with excessive production of inflammatory cytokines in the lungs. This excessive inflammatory response in the lungs is associated with the local recruitment of immune cells that create a pathogenic inflammatory loop. Together, it causes severe lung pathology, including ARDS, as well as damage to other vulnerable organs, like the heart, spleen, lymph nodes, and kidney, as well as the brain. This can rapidly progress to multiple organ exhaustion and correlates with a poor prognosis in COVID-19 patients. In this review, we focus on the crucial role of different types of IFN that underlies the progression of SARS-CoV-2 infection and leads to immune cell hyper-activation in the lungs, exuberant systemic inflammation, and multiple organ damage. Consequently, to protect from systemic inflammation, it will be critical to interfere with signaling cascades activated by IFNs and other inflammatory cytokines. Targeting members of the STAT family could therefore be proposed as a novel therapeutic strategy in patients with severe COVID-19.
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19 ; Cytokines ; Humans ; Inflammation ; Interferons/therapeutic use ; Respiratory Distress Syndrome ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Cytokines ; Interferons (9008-11-1)
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.888897
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