scholarly journals Extracellular Adenosine Diphosphate Stimulates CXCL10-Mediated Mast Cell Infiltration Through P2Y1 Receptor to Aggravate Airway Inflammation in Asthmatic Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan-Yan Gao ◽  
Zeng-Yan Gao
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Signaling Pathway ◽  
Adenosine Diphosphate ◽  
Alveolar Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
P2y1 Receptor ◽  
Extracellular Adenosine ◽  
Alveolar Epithelial ◽  
Asthmatic Patients

Asthma is an inflammatory disease associated with variable airflow obstruction and airway inflammation. This study aimed to explore the role and mechanism of extracellular adenosine diphosphate (ADP) in the occurrence of airway inflammation in asthma. The expression of ADP in broncho-alveolar lavage fluid (BALF) of asthmatic patients was determined by enzyme linked immunosorbent assay (ELISA) and the expression of P2Y1 receptor in lung tissues was determined by reverse transcription-quantitative polymerase chain reaction. Asthmatic mouse model was induced using ovalbumin and the mice were treated with ADP to assess its effects on the airway inflammation and infiltration of mast cells (MCs). Additionally, alveolar epithelial cells were stimulated with ADP, and the levels of interleukin-13 (IL-13) and C-X-C motif chemokine ligand 10 (CXCL10) were measured by ELISA. We finally analyzed involvement of NF-κB signaling pathway in the release of CXCL10 in ADP-stimulated alveolar epithelial cells. The extracellular ADP was enriched in BALF of asthmatic patients, and P2Y1 receptor is highly expressed in lung tissues of asthmatic patients. In the OVA-induced asthma model, extracellular ADP aggravated airway inflammation and induced MC infiltration. Furthermore, ADP stimulated alveolar epithelial cells to secrete chemokine CXCL10 by activating P2Y1 receptor, whereby promoting asthma airway inflammation. Additionally, ADP activated the NF-κB signaling pathway to promote CXCL10 release. As a “danger signal” extracellular ADP could trigger and maintain airway inflammation in asthma by activating P2Y1 receptor. This study highlights the extracellular ADP as a promising anti-inflammatory target for the treatment of asthma.

scholarly journals miR-145 plays a role in mitochondria dysfunction in alveolar epithelial cells in LPS-induced ARDS

2019 ◽  
Author(s):  
Yi Han ◽  
Sucheng Mu ◽  
Jianli Wang ◽  
Wei Wei ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Target Genes ◽  
Intratracheal Instillation ◽  
Alveolar Epithelial Cells ◽  
Ras Signaling ◽  
Regulation Of Transcription ◽  
Mitochondria Dysfunction ◽  
Alveolar Epithelial ◽  
Ras Signaling Pathway

Abstract Backgrounds: Acute respiratory distress syndrome (ARDS) causes substantial mortality worldwide. Alveolar epithelium is one of the main sites of cell injury in ARDS. MicroRNAs (miRNAs) are small noncoding RNA molecules that are recognized as endogenous physiological regulators of gene expression. As an important miRNA, miR-145 has been studied in various diseases, while its role in ARDS remains not investigated. Methods: Intratracheal instillation of LPS was used to establish ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF), lung wet/dry ratio as well as the pathological structures using H&E staining and Transmission electron microscope (TEM) was evaluated; lung miR-145 mRNA expression was detected using qPCR. And further bioinformatics was focused on the target genes and possible pathways of the gene regulation. Results: A rat model of LPS-induced ARDS was well established by intratracheal instillation of LPS. miR-145 was down-regulated in LPS-induced ARDS lung, and mitochondria dysfunction was observed in alveolar epithelial cells in ARDS lung, most obviously at 72h after LPS. TargetScan and MirDB were used to predict the target genes of miR-145, a total of 428 overlapping genes were identified, among which, 7 genes were associated with mitochondria function. The KEGG pathways were significantly enriched in MAPK signaling pathway and RAS signaling pathway, and the GO biological process terms were mainly enriched in gene binding, signal transduction, and regulation of transcription. Conclusions: The current work provided evidence between miR-145 and LPS-induced ARDS. Clearly, miR-145 was down-regulated in LPS induced lung injury, and resultant had impact on its downstream genes targeting mitochondria functions through MAPK and RAS signaling pathway.

scholarly journals Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation

2021 ◽  
Vol 22 (2) ◽  
pp. 557
Author(s):  
Floriana Cappiello ◽  
Veronica Carnicelli ◽  
Bruno Casciaro ◽  
Maria Luisa Mangoni
Keyword(s):  
Epithelial Cells ◽  
Infectious Diseases ◽  
Wound Repair ◽  
Alveolar Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Negative Bacterium ◽  
Scratch Assay ◽  
Alveolar Epithelial ◽  
Persistent Infections ◽  
Lung Tissue Damage

Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.

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