Important Role of the IL-32 Inflammatory Network in the Host Response against Viral Infection

Zhou, Yaqin; Zhu, Ying

doi:10.3390/v7062762

Cited by 29 publications

(30 citation statements)

References 82 publications

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“…These data are also in agreement with other group's findings, showing that COX-2/PGE 2 production inhibits viral replication via the upregulation of antiviral cytokines (i.e. IL-32, IL-27, IFN-λ1) [30][31]49] in A549 cells. In contrast to our observation, it has been reported that inhibition of COX-2 and PGE 2 enhanced antiviral activity against virus infection in various kinds of cells [50][51][52].…”

Section: Discussionsupporting

confidence: 93%

Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

Lin

Yen

et al. 2016

PLoS ONE

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Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble control and G6PD-knockdown (G6PD-kd) A549 cells upon tumor necrosis factor-α (TNF-α) stimulation. A decreased expression pattern of induced COX-2 and reduced production of downstream PGE2 occurred upon TNF-α stimulation in G6PD-kd A549 cells compared with scramble control A549 cells. TNF-α-induced antiviral activity revealed that decreased COX-2 expression enhanced the susceptibility to coronavirus 229E infection in G6PD-kd A549 cells and was a result of the decreased phosphorylation levels of MAPK (p38 and ERK1/2) and NF-κB. The impaired inflammatory response in G6PD-kd A549 cells was found to be mediated through NADPH oxidase (NOX) signaling as elucidated by cell pretreatment with a NOX2-siRNA or NOX inhibitor, diphenyleneiodonium chloride (DPI). In addition, NOX activity with TNF-α treatment in G6PD-kd A549 cells was not up-regulated and was coupled with a decrease in NOX subunit expression at the transcriptional level, implying that TNF-α-mediated NOX signaling requires the participation of G6PD. Together, these data suggest that G6PD deficiency affects the cellular inflammatory response and the decreased TNF-α-mediated antiviral response in G6PD-kd A549 cells is a result of dysregulated NOX/MAPK/NF-κB/COX-2 signaling.

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Section: Discussionsupporting

confidence: 93%

Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

Lin

Yen

et al. 2016

PLoS ONE

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“…Moreover, cytokines related to cytokine release syndrome (such as IL-1A/B, IL-6, IL-10, IL-18, and TNFA), showed increased positive association to the severity of the disease in the blood from COVID-19 patients [49]. Another proinflammatory cytokine specifically upregulated in SARS-CoV-2 infected cells was IL-32, which together with CSF2, promotes the release of TNF and IL-6 in a continuous positive loop and therefore contribute to this cytokine storm [90]. Interestingly, IL-6, IL-7 and IL-18 were found to be upregulated in two of the four data sets of SARS-CoV-2 infected cells.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Ferrarini¹,

A²,

Rebollo³

et al. 2020

Preprint

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The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

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“…IL-32 is cytokine known to its important biological functions. Due to its proinflammatory function, IL-32 induces production of different chemokines and pro-inflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-8, and macrophage inflammatory protein-2 (MIP-2) and activation of the p38 mitogen-activated protein kinase (MAPK), nuclear factor κB (NF-κB), and activator protein-1 (AP-1) signaling pathways (27). IL-32 plays role in genesis and progression of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

IL-32 expression associated with lymph vessel invasion in intestinal type of gastric cancer

et al. 2020

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Background/Aim. Gastric cancer (GC) is fourth most frequent malignant tumor worldwide, frequently diagnosed at advanced stages with poor prognosis. The aim of study was to determine expression of IL-32, pro-inflammatory and angiogenic mediators in tumor, peritumor and healthy tissue, in patients with intestinal gastric cancer and the relationship with disease severity. Methods. The tissue samples of intestinal types of tumor of 60 patients with gastric cancer were analyzed. Expression of IL-32, Vascular endothelial growth factor (VEGF), IL-17 and CD31 were measured by immunohistochemistry. Results. IL-32, VEGF and IL-17 expression as well as microvascular density (MVD) were diminished in adjacent tumor tissues compared with tumor tissues. Further, more intense expression of IL-32 and VEGF and enhanced MVD were noticed in patients with severe (TNM stages III and IV) and more progressive GC (lymph vessel invasion). Conclusions. Higher expression of IL-32, VEGF and intense MVD in tumor tissue of GC patients with detectable lymph vessel invasion may be considered as a sign of the tumor's malignant progression. This emphasizes on protumorogenic and proangiogenic role of IL-32 in biology of intestinal type of gastric cancer. ApstraktUvod/Cilj. Karcinom želuca (engl. Gastric cancer-GC) je četvrti najčešći maligni tumor širom sveta, često dijagnostikovan u naprednim stadijumima sa lošom prognozom. Cilj studije je bio da se utvrdi ekspresija IL-32, pro-inflamatornih i angiogenih medijatora u tumoru, peritumoru i zdravom tkivu kod pacijenata sa intestinalnim tipom karcinoma želuca kao i povezanost sa težinom bolesti. Metode. Uzorci tkiva intestinalnog tipa tumora od 60 pacijenata sa karcinomom želuca su analizirani u studiji. Ekspresija IL-32, Vaskularnog endotelnog faktora rasta (engl. Vascular endothelial growth factor-VEGF), IL-17 i CD31 je merena imunohistohemijskom metodom. Rezultati. Ekspresija IL-32, VEGF-a i IL-17 kao i mikrovaskularna gustina (engl. Microvascular density-MVD) su smanjeni u peri-tumorskom tkivu u poređenju sa tumorskim tkivom. Intenzivnija ekspresija IL-32 i VEGF-a i pojačana MVD registrovani su kod pacijenata sa težim (TNM stadijumi III i IV) i progresivnijim karcinomom želuca (prisutna invazija limfnih sudova). Zaključak. Veća ekspresija IL-32, VEGF-a i intenzivnija MVD u tumorskom tkivu bolesnika sa karcinomom želuca i prisutnom invazijom limfnih sudova može se smatrati znakom progresije maligne bolesti. Ovaj rezultat ukazuje na protumorogenu i proangiogenu ulogu IL-32 u biologiji intestinalnog tipa karcinoma želuca.Ključne reči: karcinom želuca, IL-32, VEGF, IL-17, MVD

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Important Role of the IL-32 Inflammatory Network in the Host Response against Viral Infection

Cited by 29 publications

References 82 publications

Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

Diminished COX-2/PGE2-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

IL-32 expression associated with lymph vessel invasion in intestinal type of gastric cancer

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