scholarly journals Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation to Protect against Bacterial Infections

2018 ◽  
Author(s):  
Hayden H. Ware ◽  
Vikram V. Kulkarni ◽  
Yongxing Wang ◽  
Miguel Leiva Juarez ◽  
Carson T. Kirkpatrick ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bacterial Infections ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Lung Epithelial Cells ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Bacterial Killing ◽  
Inducible Resistance ◽  
Lung Epithelial

ABSTRACTPneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs’ mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against bacterial pathogens and provide mechanistic insights into means to protect vulnerable patients against lethal infections.

scholarly journals Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0208216 ◽  
Author(s):  
Hayden H. Ware ◽  
Vikram V. Kulkarni ◽  
Yongxing Wang ◽  
Jezreel Pantaleón García ◽  
Miguel Leiva Juarez ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bacterial Infections ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Lung Epithelial ◽  
Epithelial Resistance

scholarly journals Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Carson T. Kirkpatrick ◽  
Yongxing Wang ◽  
Miguel M. Leiva Juarez ◽  
Pooja Shivshankar ◽  
Jezreel Pantaleón García ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Type I Interferon ◽  
Reactive Oxygen ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Oxygen Species ◽  
Inducible Resistance ◽  
Lung Epithelial

ABSTRACTViral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability.IMPORTANCEViruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms.

Light-Excited Antibiotics for Potentiating Bacterial Killing via Reactive Oxygen Species Generation

2020 ◽  
Vol 12 (14) ◽  
pp. 16150-16158 ◽  
Author(s):  
Qi Jiang ◽  
Fangjie E ◽  
Jingxiao Tian ◽  
Jiangtao Yang ◽  
Jiangyan Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bacterial Killing

scholarly journals Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Arif Malik ◽  
Misbah Sultana ◽  
Aamer Qazi ◽  
Mahmood Husain Qazi ◽  
Gulshan Parveen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Radiation Therapy ◽  
Cancer Stem Cells ◽  
Ionizing Radiation ◽  
Malignant Tumors ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ros Scavenging

Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

scholarly journals High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

2015 ◽  
Vol 35 (3) ◽  
pp. 1008-1022 ◽  
Author(s):  
Xiaowen Kang ◽  
Fanwu Kong ◽  
Xiaomei Wu ◽  
Yeping Ren ◽  
Shijie Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Human Lung ◽  
Reactive Oxygen ◽  
Lung Epithelial Cells ◽  
Oxygen Species ◽  
Lung Epithelial ◽  
Tgf Β1 ◽  
Human Lung Epithelial Cells

Background: Growing evidence indicates that heme oxygenase-1 (HO-1) is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG) levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS) production and TGF-β1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS) and transforming growth factor-β1 (TGF-β1) in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC) or with phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β1/PI3K/Akt signaling pathway.

scholarly journals Erratum for Kirkpatrick et al., “Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections”

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Carson T. Kirkpatrick ◽  
Yongxing Wang ◽  
Miguel M. Leiva Juarez ◽  
Pooja Shivshankar ◽  
Jezreel Pantaleón García ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Viral Infections ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Lung Epithelial ◽  
Epithelial Resistance

Роль оксида азота в реализации антиоксидантного эффекта неопиатного аналога лей-энкефалина в сердце новорожденных белых крыс

2019 ◽  
pp. 61-64
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Postnatal Period ◽  
Oxide System ◽  
No Synthase ◽  
Albino Rats ◽  
Oxygen Species ◽  
Control Parameters ◽  
Synthase Inhibitor

The eff ect of the non-opiate analog of leu-enkephalin (peptide NALE: Phe – D – Ala – Gly – Phe – Leu – Arg) on the reactive oxygen species generation in the heart of albino rats in the early postnatal period was studied. Peptide NALE was administered intraperitoneally in the dose of 100 μ/kg daily from 2 to 6 days of life. Reactive oxygen species generation was assessed by chemiluminescence in the heart homogenates of 7-day-old animals. Decreasing of reactive oxygen species generation nearly by 30 % and an increasing in antioxidant system activity by the 20-27 %, compared with the control parameters, were found. The antioxidant eff ect of peptide NALE is associated with the presence of the amino acid Arg in the structure of the peptide. An analogue of NALE peptide, devoid of Arg (peptide Phe – D – Ala – Gly – Phe – Leu – Gly), had a signifi cant lower antioxidant eff ect. The NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the dose 50 mg/kg, administered with NALE peptide, reduced the severity of the NALE antioxidant eff ect. The results of the study suggest that the pronounced antioxidant eff ect of NALE peptide in the heart of albino rats, at least in part, is due to the interaction with the nitric oxide system.

Sign in / Sign up

Export Citation Format

Share Document