scholarly journals Diesel Exhaust Particle Exposure Compromises Alveolar Macrophage Mitochondrial Bioenergetics

2019 ◽  
Vol 20 (22) ◽  
pp. 5598
Author(s):  
Jonathan L. Gibbs ◽  
Blake W. Dallon ◽  
Joshua B. Lewis ◽  
Chase M. Walton ◽  
Juan A. Arroyo ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Diesel Exhaust ◽  
Critical Role ◽  
Cell Communication ◽  
Diesel Exhaust Particle ◽  
Diesel Exhaust Particles ◽  
The Body ◽  
Whole Body ◽  
H2o2 Production ◽  
Pulmonary Macrophages

Diesel exhaust particles (DEPs) are known pathogenic pollutants that constitute a significant quantity of air pollution. Given the ubiquitous presence of macrophages throughout the body, including the lungs, as well as their critical role in tissue and organismal metabolic function, we sought to determine the effect of DEP exposure on macrophage mitochondrial function. Following daily DEP exposure in mice, pulmonary macrophages were isolated for mitochondrial analyses, revealing reduced respiration rates and dramatically elevated H2O2 levels. Serum ceramides and inflammatory cytokines were increased. To determine the degree to which the changes in mitochondrial function in macrophages were not dependent on any cross-cell communication, primary pulmonary murine macrophages were used to replicate the DEP exposure in a cell culture model. We observed similar changes as seen in pulmonary macrophages, namely diminished mitochondrial respiration, but increased H2O2 production. Interestingly, when treated with myriocin to inhibit ceramide biosynthesis, these DEP-induced mitochondrial changes were mitigated. Altogether, these data suggest that DEP exposure may compromise macrophage mitochondrial and whole-body function via pathologic alterations in macrophage ceramide metabolism.

Gene Expression Analysis to Investigate Biological Networks Underlying Nasal Inflammatory Dysfunctions Induced by Diesel Exhaust Particles Using an In Vivo System

2019 ◽  
Vol 129 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Hyun Soo Kim ◽  
Byeong-Gon Kim ◽  
Sohyeon Park ◽  
Nahyun Kim ◽  
An-Soo Jang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Diesel Exhaust ◽  
Expression Profiles ◽  
Complex Mixture ◽  
Diesel Exhaust Particles ◽  
The Body ◽  
Exhaust Particles

Objectives: Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo. Methods: In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity. Results: Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8. Conclusions: Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.

Effects of diesel exhaust particles on macrophage polarization

2016 ◽  
Vol 36 (4) ◽  
pp. 412-420 ◽  
Author(s):  
N Labranche ◽  
C El Khattabi ◽  
G Berkenboom ◽  
S Pochet
Keyword(s):  
Mrna Expression ◽  
Diesel Exhaust ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Diesel Exhaust Particles ◽  
Western Blots ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α ◽  
Exhaust Particles

Background: Exposure to diesel exhaust particles (DEP) has long been associated with increased cardiovascular morbidity and mortality. The development of DEP toxicity seems to be linked to inflammation in which macrophages play a critical role. Macrophages can be polarized into proinflammatory M1 or anti-inflammatory M2 macrophages. The aim of this study was to identify the role of inflammation in DEP-induced toxicity by assessing the effects of DEP on macrophage polarization. Methods: Monocyte-derived macrophages (Mϕ) were stimulated with interferon γ and lipopolysaccharide or interleukin (IL)-4 to obtain M1 and M2 subtypes, respectively. To test the polarization capacity of DEP, Mϕ cells were exposed to DEP and compared to Mϕ, M1, and M2. We also studied the effects of DEP on already-polarized M1 or M2. The M1 markers assessed were tumor necrosis factor α (TNF-α) and IL-1β, while the M2 markers were the mannose receptor C type 1 (MRC-1) and transglutaminase 2 (TGM2). Results: Western blots revealed a 31 kDa band corresponding to pro-IL-1β, but only in M1-polarized macrophages. In M1, we also observed an upregulation of TNF-α messenger RNA (mRNA) expression. MRC-1 and TGM2 mRNA expression were only significantly enhanced in M2. DEP had no effect on any of the M1/M2 markers assessed. Moreover, DEP were not able to modify the phenotype of already-polarized M1 or M2. Conclusion: Mϕ incubation with DEP did not have any effect on macrophage polarization, at least on the markers assessed in this study, namely, TNF-α/IL-1β for M1, and MRC-1/TGM2 for M2. Hence, these data argue against an important role of inflammation in DEP-induced vascular toxicity.

scholarly journals Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3466
Author(s):  
Frédéric Nicolas Daussin ◽  
Alexane Cuillerier ◽  
Julianne Touron ◽  
Samir Ben Said ◽  
Bruno Melo ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Mitochondrial Function ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
H2o2 Production ◽  
Wild Type ◽  
Nad Metabolism ◽  
Whole Body Metabolism ◽  
Cocoa Flavanols

Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3-/- mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was performed to assess glucose metabolism. Mitochondrial respiratory function was assessed in permeabilised fibres and the pyridine nucleotides content (NAD+ and NADH) were quantified. In the wild type, CF supplementation significantly modified whole-body metabolism by promoting carbohydrate use and improved glucose tolerance. CF supplementation induced a significant increase of mitochondrial mass, while significant qualitative adaptation occurred to maintain H2O2 production and cellular oxidative stress. CF supplementation induced a significant increase in NAD+ and NADH content. All the effects mentioned above were blunted in Sirt3-/- mice. Collectively, CF supplementation boosted the NAD metabolism that stimulates sirtuins metabolism and improved mitochondrial function, which likely contributed to the observed whole-body metabolism adaptation, with a greater ability to use carbohydrates, at least partially through Sirt3.

scholarly journals Diesel Exhaust Particle-Induced Airway Responses are Augmented in Obese Rats

2014 ◽  
Vol 33 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Kuk-Young Moon ◽  
Moo-Kyun Park ◽  
George D. Leikauf ◽  
Choon-Sik Park ◽  
An-Soo Jang
Keyword(s):  
Diesel Exhaust ◽  
Messenger Rna ◽  
Diesel Exhaust Particle ◽  
Diesel Exhaust Particles ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Counts ◽  
Obese Rats ◽  
Long Evans ◽  
Airway Responses

Air pollutants and obesity are important factors that contribute to asthma. The aim of this study was to assess the airway responsiveness and inflammation in Otsuka-Long Evans Tokushima Fatty (OLETF) obese rats and Long Evans Tokushima-Otsuka (LETO) nonobese rats exposed to diesel exhaust particles (DEPs). Otsuka Long Evans Tokushima fatty rats and LETO rats were exposed intranasally to DEP and then challenged with aerosolized DEP on days 6 to 8. Body plethysmography, bronchoalveolar lavage (BAL), and histology were performed. Enhanced pause (Penh) was measured as an indicator of airway resistance on day 9 and samples were collected on day 10. After exposure to DEP, the OLETF group exhibited a greater increase in Penh compared to that in the LETO group. Moreover, the BAL fluid in mice showed an increase in the total and differential cell counts in the DEP-exposed OLETF group compared to that in the DEP-exposed LETO group. Histological assessment of lung tissue from each group revealed that the DEP-exposed OLETF group tended to have increased inflammatory cell infiltrations in the prebronchial area. Increased peroxisome proliferator-activated receptor γ, coactivator 1β messenger RNA was observed in the lungs of obese rats compared to that in nonobese rats following DEP exposure. These data indicate that the DEP-exposed OLETF group had increased airway responses and inflammation compared to the DEP-exposed LETO group, indicating that diesel particulates and obesity may be co-contributors to asthma.

Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells

2007 ◽  
Vol 292 (2) ◽  
pp. L422-L429 ◽  
Author(s):  
Dongsun Cao ◽  
Tamara L. Tal ◽  
Lee M. Graves ◽  
Ian Gilmour ◽  
William Linak ◽  
...  
Keyword(s):  
Growth Factor ◽  
Diesel Exhaust ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Diesel Exhaust Particles ◽  
Diesel Exhaust Particulate ◽  
Stat3 Phosphorylation

In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines and chemokines. Signal transducers and activators of transcription (STAT) proteins are a family of cytoplasmic transcription factors that are key transducers of signaling in response to cytokine and growth factor stimulation. One member of the STAT family, Stat3, has been implicated as a regulator of inflammation but has not been studied in regard to DEP exposure. The results of this study show that DEP induces Stat3 phosphorylation as early as 1 h following stimulation and that phosphorylated Stat3 translocates into the nucleus. Inhibition of epidermal growth factor receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2, respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3 activation by DEP requires EGFR and Src kinase activation. The present study suggests that oxidative stress induced by DEP may play a critical role in activating EGFR signaling, as evidenced by the fact that pretreatment with antioxidant prevented the activation of EGFR and Stat3. These findings demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in vitro.

scholarly journals Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Panjamaporn Sangwung ◽  
Kitt Falk Petersen ◽  
Gerald I Shulman ◽  
Joshua W Knowles
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Ex Vivo ◽  
Critical Role ◽  
Whole Body ◽  
Genetic Studies ◽  
Cellular Energy

Abstract Insulin resistance (IR) is fundamental to the development of type 2 diabetes (T2D) and is present in most prediabetic (preDM) individuals. Insulin resistance has both heritable and environmental determinants centered on energy storage and metabolism. Recent insights from human genetic studies, coupled with comprehensive in vivo and ex vivo metabolic studies in humans and rodents, have highlighted the critical role of reduced mitochondrial function as a predisposing condition for ectopic lipid deposition and IR. These studies support the hypothesis that reduced mitochondrial function, particularly in insulin-responsive tissues such as skeletal muscle, white adipose tissue, and the liver, is inextricably linked to tissue and whole body IR through the effects on cellular energy balance. Here we discuss these findings as well as address potential mechanisms that serve as the nexus between mitochondrial malfunction and IR.

Effects of Diesel Exhaust Particle Extracts on TH1 and TH2 Immune Responses in Mice

2002 ◽  
Vol 15 (1) ◽  
pp. 13-18 ◽  
Author(s):  
S. Yoshino ◽  
H. Hayashp ◽  
S. Taneda ◽  
H. Takano ◽  
M. Sagai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Diesel Exhaust ◽  
Diesel Exhaust Particle ◽  
Diesel Exhaust Particles ◽  
Spleen Cells ◽  
Th2 Responses ◽  
Exhaust Particles ◽  
Th1 And Th2 Responses ◽  
Th1 Immune Responses ◽  
Th1 And Th2

The present study was undertaken to investigate the effects of extracts of diesel exhaust particles (DEP) on Th1 and Th2 immune responses. In order to separate compounds from DEP different in hydrophobicity, a single DEP sample was consecutively extracted with hexane (HEX-DEP), benzene (BEN-DEP), dichloromethane (DIC-DEP), methanol (MET-DEP), and 1M ammonia (AMM-DEP). The last unextracted residue (UNE-DEP) was also used to test its effect on immune responses. To immunize mice, hen egg lysozyme (HEL) was injected i.p. (day 0). Varying doses of DEP, each DEP extract, and UNE-DEP were intranasally administered every 2 days from days 0 to 18. Anti-HEL IgG2a antibodies in sera and IFN-g secreted from spleen cells were measured as an indicator of Th1 immune responses, while anti-HEL IgG1 antibodies and IL-4 as that of Th2 responses. The results showed that treatment with DEP and DIC-DEP increased both Th1 and Th2 responses to HEL. UNE-DEP facilitated Th1 but not Th2 responses, while MET- and AMM-DEP administration was followed by enhancement of Th2 but not Th1 responses. Neither HEX- nor BEN-DEP modulated Th1 as well as Th2 responses. These results suggest that DEP contain various compounds different in hydrophobicity which may affect both Th1 and Th2, Th1 but not Th2, and Th2 but not Th1 immune responses.

scholarly journals Mitochondrial Biogenesis Induced by Exercise and Nutrients: Implication for Performance and Health Benefits

2017 ◽  
Vol 2 (2) ◽  
pp. 221
Author(s):  
Kazumi Masuda ◽  
Thomas Jue ◽  
Ronald D. Ray Hamidie
Keyword(s):  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Power Plants ◽  
The Body ◽  
Whole Body ◽  
Mitochondrial Quality Control ◽  
Disease States ◽  
Muscle Health ◽  
Metabolic Properties ◽  
Lower Physical Activity

The skeletal muscle occupies about 40% of body mass, one of the largest organs in the body, and it has great plasticity in response to physiological stressors and then alters the contractile and metabolic properties of the muscles. Therefore, healthy status of muscle affects health status of whole body. Mitochondria are abundantly present in mammalian muscle cells, known as the power plants of the cell to generate adenosine triphosphate (ATP) with oxygen. The muscle health depends on the mitochondrial function. In aging and some of metabolic disease states, the mitochondrial function is defected. Some parts of this defect result from lower physical activity and nutritional status. The exercise is well-known as a major strategy to induce mitochondrial biogenesis and upregulation of the mitochondrial function. Recently some nutrients are also suggested as ligands for transcription of the mitochondrial proteins. We also recently found insight of protein interaction with mitochondria that will possibly augment mitochondrial respiratory potential. The present review article introduces some recent research evidences relating to mitochondrial quality control, mitochondrial biogenesis mediated by both exercise and nutrients and an interaction of protein with mitochondria to facilitate mitochondrial respiration.

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