scholarly journals Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aartik Sarma ◽  
Stephanie A. Christenson ◽  
Ashley Byrne ◽  
Eran Mick ◽  
Angela Oliveira Pisco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Profiling ◽  
In Silico Analysis ◽  
Tracheal Aspirate ◽  
Expression Of Genes ◽  
Elevated Expression ◽  
Proinflammatory Gene ◽  
The Relationship ◽  
Proinflammatory Gene Expression ◽  
Stimulating Factor

AbstractThe immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a “cytokine storm,” we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

scholarly journals COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone

2021 ◽  
Author(s):  
Aartik Sarma ◽  
Stephanie Christenson ◽  
Eran Mick ◽  
Thomas Deiss ◽  
Catherine DeVoe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Response ◽  
Transcriptional Profiling ◽  
Cytokine Storm ◽  
Expression Of Genes ◽  
Elevated Expression ◽  
Proinflammatory Gene ◽  
The Relationship ◽  
Proinflammatory Gene Expression ◽  
Stimulating Factor

Abstract We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.

CCAAT/enhancer binding protein δ regulates glial proinflammatory gene expression

2013 ◽  
Vol 34 (9) ◽  
pp. 2110-2124 ◽  
Author(s):  
Tony Valente ◽  
Marco Straccia ◽  
Nuria Gresa-Arribas ◽  
Guido Dentesano ◽  
Josep M. Tusell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression

scholarly journals Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages

2013 ◽  
Vol 288 (35) ◽  
pp. 25362-25374 ◽  
Author(s):  
Melanie R. Shakespear ◽  
Daniel M. Hohenhaus ◽  
Greg M. Kelly ◽  
Nabilah A. Kamal ◽  
Praveer Gupta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression

Abstract 573: Endothelial α5 Integrins Regulate OxLDL-Induced Fibronectin Deposition, Proinflammatory Gene Expression, and Early Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Arif Yurdagul ◽  
Jonette Green ◽  
Wayne Orr
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Oxidized Ldl ◽  
Focal Adhesions ◽  
Published Data ◽  
Matrix Remodeling ◽  
Proinflammatory Gene ◽  
Fibronectin Deposition ◽  
Proinflammatory Gene Expression

Alterations in extracellular matrix quantity and composition contribute to atherosclerosis, with remodeling of the subendothelial basement membrane to a fibronectin-rich matrix preceding lesion development. Published data from our lab and others demonstrate that endothelial cell interactions with fibronectin prime inflammatory responses to a variety of atherogenic stimuli. However, the mechanisms regulating early atherogenic fibronectin accumulation remain unknown. Work from our group previously demonstrated that oxidized LDL (oxLDL) promotes endothelial proinflammatory gene expression by activating the integrin α5β1, a classic mediator of fibronectin fibrillogenesis. We now show that treating endothelial cells with oxLDL induces fibronectin deposition and inhibiting α5β1 (blocking antibodies, α5 knockout cells) completely inhibits oxLDL-induced fibronectin deposition. While endothelial fibronectin expression remains unchanged, oxLDL robustly stimulates the deposition of endothelial cell-derived fibronectin associated with a significant reduction in intracellular fibronectin. Interestingly, loss of endothelial cell-derived fibronectin, but not plasma fibronectin, prevents integrin α5 localization to focal adhesions, reduces fibronectin fibril length, and inhibits oxLDL-induced VCAM-1 expression. In addition, inducible endothelial-specific deletion of α5 integrins significantly blunts atherosclerotic plaque formation in ApoE knockout mice, suggesting an important role for this integrin in early endothelial activation. Taken together, our data demonstrate that oxLDL stimulates α5 integrin-dependent subendothelial matrix remodeling and endothelial proinflammatory gene expression through the deposition of fibronectin.

Changes in proinflammatory gene expression in human whole blood after contact with UV-conditioned implant surfaces

2019 ◽  
Vol 23 (10) ◽  
pp. 3731-3738
Author(s):  
Sönke Harder ◽  
Elgar Susanne Quabius ◽  
Fabian Meinke ◽  
Christian Mehl ◽  
Matthias Kern
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Human Whole Blood ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression
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