ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection

Othumpangat, Sreekumar; Noti, John D.; McMillen, Cynthia M.; Beezhold, Donald H.

doi:10.1016/j.virol.2015.10.005

Cited by 46 publications

(32 citation statements)

References 30 publications

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“…Intercellular adhesion molecule (ICAM)-1 is expressed on the surface of numerous classes of cells, including endothelial cells and immune cells. In addition, ICAM-1 is induced by cell factors, including IL-1, TNF-α and bacterial lipopolysacharide (27). A previous study confirmed that the synergistic effects of IL-17 and TNF-α enhance ICAM-1 expression in several inflammatory diseases (28).…”

Section: Microrna-381 Reduces Inflammation and Infiltration Of Macropmentioning

confidence: 80%

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1

et al. 2018

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The downregulation of microRNA (miR)-381 has been detected in various diseases. The present study aimed to investigate the effects, and underlying mechanisms of miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse model of experimental autoimmune myositis (EAM) was generated in this study. Hematoxylin and eosin staining was conducted to detect the inflammation of muscle tissues. In addition, ELISA and immunohistochemistry were performed to determine the expression levels of associated factors, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of related mRNAs and proteins. A luciferase activity assay was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1) 3' untranslated region. Transwell assays were also performed to assess the migratory ability of macrophages. The results demonstrated that serum creatine kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in patients with PM were increased compared within healthy controls. Conversely, the expression levels of miR-381 were downregulated in patients with PM. Furthermore, high HMGB1 expression was associated with poor survival rate in patients with PM. In the mouse studies, muscle inflammation and CD163 expression were decreased in the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule (ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These findings indicated that HMGB1 was closely associated with inflammatory responses. In addition, the present study indicated that transfection of macrophages with miR-381 mimics reduced the migration of inflammatory macrophages, and the expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition exerted the opposite effects. The effects of miR-381 inhibitors were reversed by HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and the infiltration of macrophages; these effects were closely associated with the downregulation of HMGB1.

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Section: Microrna-381 Reduces Inflammation and Infiltration Of Macropmentioning

confidence: 80%

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1

et al. 2018

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“…We detected hub genes signature (BIRC3, ICAM1, IRAK2, MAP3K8, S100A8, SOCS3, STAT5A, TNF, TNFAIP3, TNIP1) from PPI interaction network analysis. Among the hub proteins, ICAM1 has been previously demonstrated that its expression levels at the level of mRNA and protein levels increased in human bronchial epithelial cells and nasopharyngeal epithelial cells in response to influenza virus infection ( Othumpangat et al, 2016 ). More than 90% of Rhinovirus serotypes use ICAM1 as the receptor.…”

Section: Discussionmentioning

confidence: 99%

Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19

Islam

Rahman

Aydın

et al. 2020

European Journal of Pharmacology

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, more commonly COVID-19 has emerged as a world health pandemic. There are couples of treatment methods for COVID-19, however, well-established drugs and vaccines are urgently needed to treat the COVID-19. The new drug discovery is a tremendous challenge; repurposing of existing drugs could shorten the time and expense compared with de novo drug development. In this study, we aimed to decode molecular signatures and pathways of the host cells in response to SARS-CoV-2 and the rapid identification of repurposable drugs using bioinformatics and network biology strategies. We have analyzed available transcriptomic RNA-seq COVID-19 data to identify differentially expressed genes (DEGs). We detected 177 DEGs specific for COVID-19 where 122 were upregulated and 55 were downregulated compared to control (FDR<0.05 and logFC ≥ 1). The DEGs were significantly involved in the immune and inflammatory response. The pathway analysis revealed the DEGs were found in influenza A, measles, cytokine signaling in the immune system, interleukin-4, interleukin −13, interleukin −17 signaling, and TNF signaling pathways. Protein-protein interaction analysis showed 10 hub genes (BIRC3, ICAM1, IRAK2, MAP3K8, S100A8, SOCS3, STAT5A, TNF, TNFAIP3, TNIP1). The regulatory network analysis showed significant transcription factors (TFs) that target DEGs, namely FOXC1, GATA2, YY1, FOXL1, NFKB1. Finally, drug repositioning analysis was performed with these 10 hub genes and showed that in silico validated three drugs with molecular docking. The transcriptomics signatures, molecular pathways, and regulatory biomolecules shed light on candidate biomarkers and drug targets which have potential roles to manage COVID-19. ICAM1 and TNFAIP3 were the key hubs that have demonstrated good binding affinities with repurposed drug candidates. Dabrafenib, radicicol, and AT-7519 were the top-scored repurposed drugs that showed efficient docking results when they tested with hub genes. The identified drugs should be further evaluated in molecular level wet-lab experiments in prior to clinical studies in the treatment of COVID-19.

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“…The correlation between TNP1 and COVID-19 (Figure 1 and Table S2) could be due to its role in suppressing NF-kB pathway and therefore regulating the overexpression of viral proteins (Nimmerjahn et al 2004) (Ramirez, Gurevich, and Aneskievich 2012) . The ICAM-1 intercellular adhesion molecule plays a major role in the infectivity and neutralization of the HIV-I and controls the survival of the influenza virus in lung epithelial cells during the early stages of infection (Othumpangat et al 2016) . Forkhead Box O1 (FOXO1) is a transcription factor that plays an important role in the regulation of insulin signaling for gluconeogenesis and glycogenolysis.…”

Section: We Identified a Strong Association Between Covid-19 Infectiomentioning

confidence: 99%

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Alsamman

Zayed

2020

Preprint

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COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of~7% and recovery rate of~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.

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ICAM-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection

Cited by 46 publications

References 30 publications

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1

Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

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