scholarly journals Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3305
Author(s):  
Muthanna Sultan ◽  
Kiesha Wilson ◽  
Osama A. Abdulla ◽  
Philip Brandon Busbee ◽  
Alina Hall ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Tight Junction ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Epithelial Cells ◽  
Tight Junction Proteins ◽  
Sequencing Data ◽  
16S Rna ◽  
Junction Proteins

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.

scholarly journals Identification of Different Proteins Binding to Na, K-ATPase α1 in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome Cell Model by Proteomic Analysis

2021 ◽  
Author(s):  
Xu-Peng Wen ◽  
Yue-Zhong Zhang ◽  
He Huang ◽  
Tao-Hua Liu ◽  
Qi-Quan Wan
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Tight Junction ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
A549 Cell ◽  
Distress Syndrome ◽  
Cell Model ◽  
Interacting Proteins ◽  
Proteomic Approach ◽  
And Control

Abstract Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. Using an unbiased, discovery and quantitative proteomic approach, the discovery of differentially expressed proteins binding to Na, K-ATPase α1 between LPS-induced A549 cell and control-A549 group is of particular interest for the current study. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS. We screened these Na, K-ATPase α1 interacting proteins, carried out the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. We also chose some of the differentiated expressing proteins with significant performance for further verification by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). Protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. In conclusion, our quantitative discovery-based proteomic approach identified commonalities, and revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell.

scholarly journals Intestinal Collinsella may mitigate infection and exacerbation of COVID-19 by producing ursodeoxycholate

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260451
Author(s):  
Masaaki Hirayama ◽  
Hiroshi Nishiwaki ◽  
Tomonari Hamaguchi ◽  
Mikako Ito ◽  
Jun Ueyama ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Gut Microbiota ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Mortality Rates ◽  
Sequencing Data ◽  
Angiotensin Converting Enzyme 2 ◽  
Underlying Mechanisms ◽  
Apoptotic Effects

The mortality rates of COVID-19 vary widely across countries, but the underlying mechanisms remain unelucidated. We aimed at the elucidation of relationship between gut microbiota and the mortality rates of COVID-19 across countries. Raw sequencing data of 16S rRNA V3-V5 regions of gut microbiota in 953 healthy subjects in ten countries were obtained from the public database. We made a generalized linear model (GLM) to predict the COVID-19 mortality rates using gut microbiota. GLM revealed that low genus Collinsella predicted high COVID-19 mortality rates with a markedly low p-value. Unsupervised clustering of gut microbiota in 953 subjects yielded five enterotypes. The mortality rates were increased from enterotypes 1 to 5, whereas the abundances of Collinsella were decreased from enterotypes 1 to 5 except for enterotype 2. Collinsella produces ursodeoxycholate. Ursodeoxycholate was previously reported to inhibit binding of SARS-CoV-2 to angiotensin-converting enzyme 2; suppress pro-inflammatory cytokines like TNF-α, IL-1β, IL-2, IL-4, and IL-6; have antioxidant and anti-apoptotic effects; and increase alveolar fluid clearance in acute respiratory distress syndrome. Ursodeoxycholate produced by Collinsella may prevent COVID-19 infection and ameliorate acute respiratory distress syndrome in COVID-19 by suppressing cytokine storm syndrome.

scholarly journals Mechanosensitive activation of mTORC1 mediates ventilator induced lung injury during the acute respiratory distress syndrome

2020 ◽  
Author(s):  
Hyunwook Lee ◽  
Qinqin Fei ◽  
Adam Streicher ◽  
Wenjuan Zhang ◽  
Colleen Isabelle ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Epithelial Cells ◽  
Ventilator Induced Lung Injury ◽  
Lung Epithelial

AbstractAcute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation maintains gas exchange in patients with ARDS, but exposes lung cells to physical forces that exacerbate lung injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during mechanical ventilation exacerbates lung injury. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells exacerbates physiologic lung dysfunction during mechanical ventilation. Conversely, treatment with rapamycin at the time mechanical ventilation is initiated prevents physiologic lung injury (i.e. decreased compliance) without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during mechanical ventilation. Our data demonstrate that in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during mechanical ventilation exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator induced lung injury during ARDS.

scholarly journals Regeneration of lung epithelial cells by Fullerene C60 nanoformulation: A possible treatment strategy for acute respiratory distress syndrome (ARDS)

2020 ◽  
Author(s):  
Nabodita Sinha ◽  
Ashwani Kumar Thakur
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Epithelial Cells ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Respiratory Infections ◽  
Fullerene C60 ◽  
Lung Epithelial Cells ◽  
Proof Of Concept ◽  
Lung Epithelial

Acute respiratory distress syndrome (ARDS) involves death of lung epithelial cells. ARDS is a leading reason behind mortality in respiratory infections. Here we show a proof-of-concept that a Fullerene nanoformulation can be used for the regeneration of cells treated with apoptosis-inducing molecules, suggeting its potential for ARDS therapy.

COVID-19 – eine vaskuläre Systemerkrankung

2020 ◽  
Vol 49 (10) ◽  
pp. 418-421
Author(s):  
Christopher Werlein ◽  
Peter Braubach ◽  
Vincent Schmidt ◽  
Nicolas J. Dickgreber ◽  
Bruno Märkl ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.

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