scholarly journals Influenza A virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11892
Author(s):  
Tiantian Han ◽  
Yanni Lai ◽  
Yong Jiang ◽  
Xiaohong Liu ◽  
Danhua Li
Keyword(s):  
Endothelial Cells ◽  
Influenza A ◽  
H1n1 Virus ◽  
Enrichment Analysis ◽  
Microvascular Endothelial Cells ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Real Time Quantitative Pcr ◽  
Microvascular Leakage ◽  
Microvascular Endothelial ◽  
Pro Inflammatory Cytokines

Objective To investigate the replication of influenza A virus A/Puerto Rico/8/34 (H1N1) in pulmonary microvascular endothelial cells and its effect on endothelial barrier function. Methods Human pulmonary microvascular endothelial cells were infected with influenza A/Puerto Rico/8/34 (H1N1) virus. Plaque reduction assay, real-time quantitative PCR, immunofluorescence staining, and western blot were used to elucidate the replication process of virus-infected endothelial cells. In addition, real-time quantitative PCR was used to detect the relative expression levels of mRNA of some inflammatory factors. The endothelial resistance assay was used to determine the permeability of the endothelial monolayer. Excavation and analysis of data from open databases, such as the GeneCards database, DAVID Bioinformatics Resources, STRING search tool, and DGIdb database determined the genes, proteins, and signal pathways related to microvascular leakage caused by the H1N1 virus, and predicted the drugs that could be effective for treatment. Results In vitro experiments showed that the influenza virus can infect endothelial cells, leading to a significant increase in the permeability of pulmonary microvascular endothelial cells and the release of pro-inflammatory cytokines, but does not efficiently replicate in endothelial cells. A total of 107 disease-related target genes were obtained from the Gene-cards database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these genes mainly affected the pathways related to “Inflammatory bowel disease” (IBD), “Chagas disease” (American trypanosomiasis), “Influenza A”, and also played a key role in anti-inflammation and regulation of immunity. After enrichment analysis, 46 hub genes were screened. A total of 42 FDA-approved drugs corresponding to the hub genes were screened from the DGIdb database, and these could be formulated for topical application. In addition, these drugs can be used to treat other diseases, including cancer, inflammatory diseases, immune system disorders, and cardiovascular diseases. Conclusion H1N1 influenza virus affects the barrier function of endothelial cells indirectly. Combined with bioinformatics tools, we can better understand the possible mechanism of action of influenza A (H1N1) virus causing pulmonary microvascular leakage and provide new clues for the treatment of pulmonary microvascular leakage.

scholarly journals Altered Gene Expression in Human Brain Microvascular Endothelial Cells in Response to the Infection of Influenza H1N1 Virus

2021 ◽  
Author(s):  
Doaa Higazy ◽  
Xianwu Lin ◽  
Tanghui Xie ◽  
Ke Wang ◽  
Xiaochen Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Human Brain ◽  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Viruses ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Abstract Influenza viruses are not only causing respiratory illness, but also neurological manifestations were reported following acute viral infection. The Central nervous system (CNS) has a specific defence mechanism against pathogens structured by cerebral microvasculature lined with brain endothelial cells to form the blood-brain barrier (BBB). To investigate the response of human brain microvascular endothelial cells (hBMECs) to the influenza A virus, we inoculated the cells with the A/WSN/33 (H1N1) virus. We then conducted an RNAseq experiment to determine the changes in gene expression levels and the activated disease pathways following infection. The analysis revealed an effective activation of the innate immune defence by inducing the pattern recognition receptors (PRRs). Along with the production of proinflammatory cytokines, we detected an upregulation of interferons and interferon-stimulated genes, such as IFN-β/λ, ISG15, CXCL11, CXCL3, and IL-6, etc. Moreover, infected hBMECs exhibited a disruption in the cytoskeletal structure both on the transcriptomic and cellular levels. We also noted that pathways of neuroactive ligand-receptor interaction, neuroinflammation, and neurodegenerative diseases were noticeably induced together with a predicted activation of the neuroglia. Likewise, a number of genes linked with the mitochondrial structure and function display a significant differential expression. En masse, this data supports that hBMECs could be infected by the influenza A virus, which induces the innate and inflammatory immune response. The results suggest that the influenza virus infection could potentially induce a subsequent aggravation of neurological disorders.

Proproliferative phenotype of pulmonary microvascular endothelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. L671-L677 ◽  
Author(s):  
Victor Solodushko ◽  
Brian Fouty
Keyword(s):  
Endothelial Cells ◽  
Barrier Function ◽  
Pulmonary Arteries ◽  
D1 Protein ◽  
Coagulation Cascade ◽  
Microvascular Endothelial Cells ◽  
Significant Heterogeneity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Pulmonary Microcirculation

Endothelial cells perform a number of important functions including release of vasodilators, control of the coagulation cascade, and restriction of solutes and fluid from the extravascular space. Regulation of fluid balance is of particular importance in the microcirculation of the lung where the loss of endothelial barrier function can lead to alveolar flooding and life-threatening hypoxemia. Significant heterogeneity exists between endothelial cells lining the microcirculation and cells from larger pulmonary arteries, however, and these differences may be relevant in restoring barrier function following vascular injury. Using well-defined populations of rat endothelial cells harvested from the pulmonary microcirculation [pulmonary microvascular endothelial cells (PMVEC)] and from larger pulmonary arteries [pulmonary artery endothelial cells (PAEC)], we compared their growth characteristics in low serum conditions. Withdrawal of serum inhibited proliferation and induced G0/G1 arrest in PAEC, whereas PMVEC failed to undergo G0/G1 arrest and continued to proliferate. Consistent with this observation, PMVEC had an increased cdk4 and cdk2 kinase activity with hyperphosphorylated (inactive) retinoblastoma (Rb) relative to PAEC as well as a threefold increase in cyclin D1 protein levels; overexpression of the cdk inhibitors p21Cip1/Waf1 and p27Kip1 induced G0/G1 arrest. While serum withdrawal failed to induce G0/G1 arrest in nonconfluent PMVEC, confluence was associated with hypophosphorylated Rb and growth arrest; loss of confluence led to resumption of growth. These data suggest that nonconfluent PMVEC continue to proliferate independently of growth factors. This proliferative characteristic may be important in restoring confluence (and barrier function) in the pulmonary microcirculation following endothelial injury.

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