screening-bioactive-nanoparticles-phagocytic-immune-cells-for

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Pharmacological regulation of Toll-like receptor (TLR) responses holds great promise in the treatment of many inflammatory diseases. However, there have ...

Shanghai Jiaotong University School of Medicine

Asthma exacerbations are often triggered by air pollution, including O3, whereas how patients with asthma exacerbations react to high levels of ambient ozone remain unknown. Here, we investigated the manner in which acute ozone exposure affects the pathophysiological characteristics of an asthma model on the premise of culminated allergic airway inflammation. The asthma model was constructed in mice, and enhanced pause (Penh), total and differential cell number, soluble mediator concentration, histopathology, and Muc5ac mRNA expression in the mice were observed. The results showed that ozone could induce airway hyperresponsiveness (AHR) in controls and an additional enhancement of preexisting AHR in asthmatic mice. When exposed to ozone, the asthmatic mice expressed more neutrophils, TNF-α, IL-13, and hyaluronan in bronchoalveolar lavage than controls. The mice with asthma and the controls both showed decreased epithelial cell density in the proximal and distal airways. Ozone aggravated the increased mucus production and mucin gene expression in mice with asthma. These results show that subjects with asthma may react differently to the same high level of ambient ozone, especially for those with asthma exacerbations.

Effects of acute ozone exposure on lung peak allergic inflammation of mice.

Ozone exposure worsens the development of allergen-induced asthma. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in the development of the inflammatory response, airway hyperresponsiveness (AHR) and airway remodelling. In this study, the role of the p38 MAPK pathway on the effects of chronic ozone exposure in ovalbumin (OVA)-sensitized and -challenged mice was investigated.

Activation of p38 mitogen-activated protein kinase in ovalbumin and ozone-induced mouse model of asthma.

Molecular mechanisms involved in the oxidative stress induced glucocorticoids insensitivity remain elusive. The mitogen-activated protein kinase phosphatase (MKP) 1 mediates a part of glucocorticoids action and can be modified by exogenous oxidants. Whether oxidant ozone (O3) can affect the function of MKP-1 and hence blunt the response to corticotherapy is not clear.

Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1.

To explore the impact of ozone on the airway hyperresponsinveness (AHR), airway inflammation and mucus production in an allergic asthma mouse model.

[Effects of ozone oxidative stress on the airway hyperresponsiveness and mucus production in mice with acute allergic airway inflammation].

Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks. Sodium hydrogen sulfide (NaHS), an H2S donor, was administered to the mice either before ozone exposure (preventive effect) or after completion of 6 weeks of ozone exposure (therapeutic effect). The ozone-exposed mice developed emphysema, measured by micro-computed tomography and histology, airflow limitation, measured by the forced maneuver system, and increased lung inflammation with augmented IL-1β, IL-18, and matrix metalloproteinase-9 (MMP-9) gene expression. Ozone-induced changes were associated with increased Nod-like receptor pyrin domain containing 3 (NLRP3)-caspase-1 activation and p38 mitogen-activated protein kinase phosphorylation and decreased Akt phosphorylation. NaHS both prevented and reversed lung inflammation and emphysematous changes in alveolar space. In contrast, NaHS prevented, but did not reverse, ozone-induced airflow limitation and bronchial structural remodeling. In conclusion, NaHS administration prevented and partially reversed ozone-induced features of lung inflammation and emphysema via regulation of the NLRP3-caspase-1, p38 mitogen-activated protein kinase, and Akt pathways.

Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice.

Autophagy, a catabolic process by which cytoplasmic components are degraded in lysosomes, plays an important role in the maintenance of cellular homeostasis. Dysregulation of autophagy is associated with several diseases. However, few studies have addressed the role of autophagy in the lung, and its role in lung diseases remains unclear. In the present study, we examined the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on autophagy in A549 cells and explored the underlying mechanisms. We showed that TRAIL promoted autophagosome formation, as detected by the levels of LC3-II, and its effect on promoting autophagy was dependent on the expression of the autophagy related genes (ATGs) Atg5, Atg7, and beclin-1. TRAIL-induced ATG expression was attenuated by JNK silencing or treatment with the JNK inhibitor SP600125, indicating the involvement of the JNK pathway. Crosstalk between autophagy and apoptosis was demonstrated by silencing the autophagy related genes Atg5, Atg7, and beclin-1, and the dependence of TRAIL-induced apoptosis on autophagy-related gene expression. Taken together, our results indicate that TRAIL promotes autophagy in A549 cells via a mechanism involving the modulation of ATG expression through the JNK pathway. Inhibition of autophagy enhanced TRAIL-induced cell proliferative inhibition and apoptosis in A549 cells.

Autophagy is a regulator of TRAIL-induced apoptosis in NSCLC A549 cells.

Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy.

Article	Year
Effects of acute ozone exposure on lung peak allergic inflammation of mice. Frontiers in bioscience (Landmark edition)\| PubMed ID: 23747851	2013
Activation of p38 mitogen-activated protein kinase in ovalbumin and ozone-induced mouse model of asthma. Respirology (Carlton, Vic.)\| PubMed ID: 24188200	2013
Impact of ozone exposure on the response to glucocorticoid in a mouse model of asthma: involvements of p38 MAPK and MKP-1. Respiratory research\| PubMed ID: 25287866	2014
[Effects of ozone oxidative stress on the airway hyperresponsiveness and mucus production in mice with acute allergic airway inflammation]. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases\| PubMed ID: 26269305	2015
Hydrogen Sulfide Prevents and Partially Reverses Ozone-Induced Features of Lung Inflammation and Emphysema in Mice. American journal of respiratory cell and molecular biology\| PubMed ID: 26731380	2016
Autophagy is a regulator of TRAIL-induced apoptosis in NSCLC A549 cells. Journal of cell communication and signaling\| PubMed ID: 28101818	2017
MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology\| PubMed ID: 28427045	2017

Aihua Bao

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