Figure - uploaded by Kymberly M Gowdy
Content may be subject to copyright.
Antioxidants can increase glutathione (GSH) and decrease hemeoxygenase 1 (HO-1) expression during DE enhanced influenza infection. A) Levels of GSH were quantified in PCA lung homogenates by HPLC and expressed as nmol of GSH per gram of lung tissue. Graph is representative of day 4 p.i. B) Levels of HO-1 mRNA were quantified in lung homogenates by real-time RT-PCR and normalized to levels of β-actin in mice exposed to air on day 4 p.i. (p < 0.05, n = 6).
Source publication
Numerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice we...
Contexts in source publication
Context 1
... of the mechanisms for NAC- mediated decrease in oxidative stress is to upregulate the amount of reduced glutathione (GSH) available for detoxifying reactive species [46]. Mice given NAC before all treatments had an increase in lung GSH levels and this was significant in mice exposed to DE or DE/flu at day 1 and 4 p.i. (Day 4 represented in Figure 5A). HO-1 mRNA expression after 1 or 4 days of DE exposure was also elevated in the mice exposed to DE during influ- enza infection and this was ameliorated with NAC treat- ment. ...Similar publications
Rheumatoid arthritis (RA) is one of the common autoimmune diseases, which affected by genetic and
environmental factors. IL-12 is important cytokine that play an effective role in the inflammatory reaction
of RA. It regulates the balance between Th1 and Th2 cells. Gene polymorphism of cytokines may
predispose to susceptibility and severity of RA. T...
Citations
... Other studies have used diesel exhaust particles (DEP) to mimic AP exposure. Gowdy et al. (2010) evaluated the effects of diesel emission particle (DEP) exposure throughout an influenza infection in mice. Treatment with NAC (320 mg/kg, intraperitoneal) reduced glutathione in the lungs and decreased the number of polymorphonuclear cells earlier than in untreated mice. ...
Introduction: Air pollution (AP) significantly contributes to morbidity and mortality worldwide. N-acetylcysteine (NAC) is a potent antioxidant with potential health benefits to people residing in poor air quality areas. Our study aimed to analyze animal studies conducted on rats and mice to assess the anti-inflammatory effects of NAC during exposure to air pollutants. Methods: A systematic search on two large databases was performed. Nineteen studies were included in this review following a screening of duplicates and a full-text review. Results: We found that NAC successfully ameliorates some pollution-associated inflammatory pathways. Discussion: NAC is a potential therapeutic drug against inflammatory pathologies caused by AP, although its role in human models requires further studies.
... Due to kinetics of immune mediator release after exhaust exposure, wherein the greatest immune responses in a previous study were found 3-6 h after exposure with decreases back to baseline levels observed by 24 h [89], a decrease after a single day of exposure could be explained as immune mediators being "used up". However, with the depletion effect ongoing after 8 days of exhaust exposure, combined with the decrease in neutrophil numbers in all groups, even if this decrease was only statistically significant for Canola and ULSD, this instead suggests an inability for the mouse immune system to cope with ongoing exhaust exposure, which could have serious consequences for cancer and infection [90][91][92][93]. These findings have been mirrored in a diesel exhaust human exposure study of occupationally exposed workers [90], which found workers exposed to high amounts of exhaust for prolonged periods showed immune dysregulation and decreases in serum inflammatory mediators, such as IL-8 and MIP-1β. ...
... This excluded both the histology data and lung function measurements at FRC due to different sets of mice being used for different measurements, and the mice used for airway morphometry measurements were not the same group as those used for the remainder of the results. To not overfit the model with the highly correlated cytokine data, 6 cytokines were chosen for analysis: IL-6, IL-10, G-CSF, KC, MIP-1α, and TNF-α chosen for either their importance to the innate immune response or for the observed significant differences compared to air-exposed controls [88][89][90][91][92][93][94]. Before completing the RDA, data were standardized using the command "decostand" to help account for different units of measurement used for different values [116,117]. ...
Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels. Male BALB/c mice (n = 24 per group) were exposed for 2 h/day for 8 days to diluted exhaust from a diesel engine running on ultra-low sulfur diesel (ULSD) or Tallow or Canola biodiesel, with room air exposures used as control. A variety of respiratory-related end-point measurements were assessed, including lung function, responsiveness to methacholine, airway inflammation and cytokine response, and airway morphometry. Exposure to Tallow biodiesel exhaust resulted in the most significant health impacts compared to Air controls, including increased airway hyperresponsiveness and airway inflammation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer negative health effects. Exposure to ULSD resulted in health impacts between those of the two biodiesels. The health effects of biodiesel exhaust exposure vary depending on the feedstock used to make the fuel.
... 65 In an experiment of H3N2-infected mice, N-acetylcysteine decreased pulmonary responsiveness and increased immune cytokine expression of IFN-γ in comparison to saline controls, with no effect on virus titers and expression of IL-4, IL-13, and IL-12p40. 66 ...
The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.
... However, increases in pollutant-induced oxidative stress, which has been observed after diesel exhaust, PM, and ozone exposures, 73 can result in epithelial cell damage, limiting their capacity to function. 7,9,74,75 Release of cytokines and chemokines, which recruit and activate immune cells, is also critical for coordinated innate and adaptive immune responses. 76 These include IFN-inducible cytokines, such as C-X-C motif chemokine ligand (CXCL)9/ monokine induced by IFN-g, CXCL10/IFN-g-induced protein 10, and CXCL12/stromal cell-derived factor 1 alpha, as well as neutrophil chemokines (CXCL8/IL-8 and CXCL1/GROa), lymphocyte chemoattractants (C-C motif chemokine ligand 5/ RANTES and CXCL16), and monocyte chemoattractants (C-C motif chemokine ligand 2/monocyte chemoattractant protein 1). ...
Air pollutants are a major source of increased risk of disease, hospitalization, morbidity, and mortality worldwide. The respiratory tract is a primary target of potential concurrent exposure to both inhaled pollutants and pathogens, including viruses. While there are a variety of associative studies linking adverse outcomes to co- or subsequent exposures to inhaled pollutants and viruses, knowledge about causal linkages and mechanisms by which pollutant exposure may alter human respiratory responses to viral infection is more limited. In this article, we review what is known about the impact of pollutant exposure on anti-viral host defense responses and describe potential mechanisms by which pollutants can alter the viral infection cycle. This review focuses on evidence from human observational and controlled exposure, ex vivo, and in vitro studies. Overall, there are a myriad of points throughout the viral infection cycle that inhaled pollutants can alter to modulate appropriate host-defense responses. These alterations may contribute to observed increases in rates of viral infection and associated morbidity and mortality in areas of the world with high ambient pollution levels or in people using tobacco products. While the understanding of mechanisms of interaction is advancing through controlled in vivo and in vitro exposure models, more studies are needed as emerging infectious pathogens, like SARS-CoV2, present a significant threat to public health.
... Studies exposing mice and rats to DE concentrations between 500 and 1000 μg/m 3 found oxidative stress and increased inflammation in the lungs of rats exposed to 950 μg/m 3 for < 1 week (Tsukue et al. 2010), increased neuroinflammation in mice exposed to 650 μg/m 3 for 4 weeks (similar to that found in 2000 μg/m 3 exposure concentrations) (Levesque et al. 2011b), increased flu severity in mice exposed to 500 μg/m 3 for < 2 weeks (Gowdy et al. 2010) and an increased effect of chemically induced arrhythmia in hypertensive rats exposed to 500 μg/m 3 for < 1 week (Hazari et al. 2015). Increased respiratory inflammation was found in allergic mice, but not healthy mice, exposed for < 1 week and the effects were lower than that found in mice exposed to 2000 μg/m 3 , suggesting dose-response relationships in these particular outcomes (Stevens et al. 2008). ...
Diesel exhaust emissions and exposure of workers in occupational settings are topics which have attracted increased attention after IARC classification as a group 1 carcinogen (IARC. Agents classified by the IARC monographs, Vols. 1–120. International Agency for the Research on Cancer. http://monographs.iarc.fr/ENG/Classification/. Accessed 21 Feb 2018; 2018). There is ongoing debate over appropriate exposure limits for occupationally exposed workers. This review consolidates recent research findings relevant to setting appropriate exposure limits, with a specific focus on newer engine and after-treatment technologies. Appropriate online databases were searched for studies published since 2005 focussing on the health effects of whole diesel exhaust exposure. Engines that used exhaust after-treatment devices including both a diesel oxidation catalyst and a diesel particulate filter were classified as new technology engines. All other studies were classified as using older technology engines. Exposure to diesel exhaust from both engine classifications resulted in negative health impacts on the lungs, heart and brain. Study participants with asthma, allergy or respiratory disease were more at risk of negative effects caused by diesel exhaust exposure than healthy subjects. Based on the published literature, an occupational limit of an average diesel exhaust concentration below 50 μg/m³ of diesel exhaust particles, 35 μg/m³ of elemental carbon, is appropriate to limit health effects. To meet this limit, many diesel engines will need to be equipped with after-treatment technology such as a DPF. However, the use of a DPF had little to no impact on measured health effects despite the removal of over 90% by weight of particles. This negates the feasibility of using particle mass-based limits.
... Air pollution exposure is associated with higher rates of hospitalizations and deaths from respiratory tract infections (2)(3)(4)(5). Multiple studies have shown that elevated levels of air pollutants such as particulate matter (PM) and nitrogen dioxide (NO 2 ) impair the innate immune response and lead to both increased susceptibility to viruses and more severe viral infections (4,6,7). Experimental studies conducted in humans indicate that air pollution damages cilia in the respiratory tract, the first line of defense against respiratory infections, and causes oxidative stress that may increase epithelial permeability (4,6,8,9). ...
... Additionally, several in vitro assays have shown that PM exposure in human respiratory epithelial cells increases the susceptibility to influenza infection by promoting viral attachment and entry. Additionally, PM affects NLRP3 inflammasome and antiviral responses by affecting ROS (Jaspers et al. 2005;Hirota et al. 2015b), through depletion of glutathione in dendritic cells, which downregulates IL-12 production and increases IL-4, favoring a Th2 phenotype (Gowdy et al. 2010). ...
Air pollution is an important cause of non-communicable diseases globally with particulate matter (PM) as one of the main air pollutants. PM is composed of microscopic particles that contain a mixture of chemicals and biological elements that can be harmful to human health. The aerodynamic diameter of PM facilitates their deposition when inhaled. For instance, coarse PM having a diameter of < 10 μm is deposited mainly in the large conducting airways, but PM of < 2.5 μm can cross the alveolar-capillary barrier, traveling to other organs within the body. Epidemiological studies have shown the association between PM exposure and risk of disease, namely those of the respiratory system such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD). However, cardiovascular and neurological diseases have also been reported, including hypertension, atherosclerosis, acute myocardial infarction, stroke, loss of cognitive function, anxiety, and Parkinson’s and Alzheimer’s diseases. Inflammation is a common hallmark in the pathogenesis of many of these diseases associated with exposure to a variety of air pollutants, including PM. This review focuses on the main effects of PM on human health, with an emphasis on the role of inflammation.
... (12). Además, se ha demostrado que las condiciones que alteran el equilibrio redox celular, ya sea por déficit de antioxidantes o aumento de radicales libres, pueden contribuir a la patogenicidad viral (11,(13)(14)(15)(16)(17). ...
Durante la infección por virus RNA se generan mecanismos oxidativos intracelulares como especies reactivas de oxígeno (ROS) y citocinas prooxidantes. Los virus RNA requieren la presencia de moléculas redox en la membrana celular para realizar los cambios conformacionales necesarios en la unión y penetración a la célula. Además, necesitan inducir estrés oxidativo celular ya que esto permite la expresión de la maquinaria bioquímica necesaria para su traducción utilizando los sitios de entrada de ribosomas internos (IRES). La generación de ROS, como consecuencia de la infección viral o por agentes xenobióticos, estimula la activación de la vía NF-κB y junto con la actividad oxidativa aumentan la replicación viral. Igualmente, los virus RNA inhiben enzimas antioxidantes como la superóxido dismutasa y factores importantes en las vías anti-inflamatorias como Nrf2, PPARγ, entre otros. El tratamiento y uso de antioxidantes como agentes terapéuticos en enfermedades virales, tanto en animales como en pacientes humanos, afecta el plegamiento de los virus durante la unión a los receptores y disminuye la generación de viriones por célula, permitiendo de esta manera la producción sostenida de antígenos virales para desarrollar una inmunidad eficiente y equilibrada.
... 229,230 In fact, in vivo studies indicate that PM exposure promotes allergic airway inflammation and increases viral replication in the lungs. [231][232][233] Thus, researchers have concluded that exposure to PM potentiates T H 2 and T H 17 responses, which are observed in asthma and allergy, dysregulating antiviral protective T H 1 responses. 135,234 The mechanism by which PM exposure promotes allergic immune responses is unclear. ...
... However, maintaining sufficient antioxidant nutrients in the diet (vitamins C and E, etc.) can protect against pollutant-induced oxidative stress and virus-induced inflammatory tissue damage. 232,262 However, the hypotheses mentioned here should be tested experimentally; thus, additional research on the effects of pollutant exposure on SARS-CoV-2 infection is required to better understand the current pandemic and combat future outbreaks. ...
Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS‐CoV‐2 infection and COVID‐19–associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID‐19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD‐19–associated immunopathology, enhancing virus‐induced tissue inflammation and damage.
... Several murine studies showing altered airway immune responses to virus infections resulting in increased inflammation and/or impaired lung function. [128][129][130][131] One study looking at DEP exposure and virus titers showed that the combination of DEP and influenza infection results in increased lung neutrophils, increased influenza virus titers, and reduced lung function compared with mice exposed to DEP or influenza alone. 131 In this study lung impairment was not significantly different between DEP/influenza-exposed vs influenza alone-exposed mice, suggesting that the virus infection exerts the most significant lung damage. ...
Asthma is a complex inflammatory disease with many triggers. The best understood asthma inflammatory pathways involve signals characterized by peripheral eosinophilia and elevated immunoglobulin E levels (called T2-high or allergic asthma), though other asthma phenotypes exist (eg, T2-low or non-allergic asthma, eosinophilic or neutrophilic-predominant). Common triggers that lead to poor asthma control and exacerbations include respiratory viruses, aeroallergens, house dust, molds, and other organic and inorganic substances. Increasingly recognized non-allergen triggers include tobacco smoke, small particulate matter (eg, PM 2.5 ), and volatile organic compounds. The interaction between respiratory viruses and non-allergen asthma triggers is not well understood, though it is likely a connection exists which may lead to asthma development and/or exacerbations. In this paper we describe common respiratory viruses and non-allergen triggers associated with asthma. In addition, we aim to show the possible interactions, and potential synergy, between viruses and non-allergen triggers. Finally, we introduce a new clinical approach that collects exhaled breath condensates to identify metabolomics associated with viruses and non-allergen triggers that may promote the early management of asthma symptoms.
