TF-343 Alleviates Diesel Exhaust Particulate-Induced Lung Inflammation via Modulation of Nuclear Factor-<i>κ</i>B Signaling

Kim, Dong Im; Song, Mi‐Kyung; Kim, Seung‐Chul; Park, Chan Young; Lee, Kyuhong

doi:10.1155/2019/8315845

Cited by 16 publications

(25 citation statements)

References 56 publications

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“…It is also important to note that many urban regions worldwide exceed 100 μg/m 3 daily PM 2.5 levels [ 80 ]. While the dose chosen for the current study may be higher than that experienced by typical human environmental exposures, the (inflammatory) findings in the lung are in agreement with previous DEP-exposure studies [ 79 , 81 , 82 ]. Furthermore, the use of this DEP material is not necessarily representative of all traffic- or industry-generated PM, by current engine standards.…”

Section: Discussionsupporting

confidence: 87%

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet

et al. 2021

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Background Exposure to traffic-generated emissions is associated with the development and exacerbation of inflammatory lung disorders such as chronic obstructive pulmonary disorder (COPD) and idiopathic pulmonary fibrosis (IPF). Although many lung diseases show an expansion of Proteobacteria, the role of traffic-generated particulate matter pollutants on the lung microbiota has not been well-characterized. Thus, we investigated the hypothesis that exposure to diesel exhaust particles (DEP) can alter commensal lung microbiota, thereby promoting alterations in the lung’s immune and inflammatory responses. We aimed to understand whether diet might also contribute to the alteration of the commensal lung microbiome, either alone or related to exposure. To do this, we used male C57Bl/6 mice (4–6-week-old) on either regular chow (LF) or high-fat (HF) diet (45% kcal fat), randomly assigned to be exposed via oropharyngeal aspiration to 35 μg DEP, suspended in 35 μl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. A separate group of study animals on the HF diet was concurrently treated with 0.3 g/day of Winclove Ecologic® Barrier probiotics in their drinking water throughout the study. Results Our results show that DEP-exposure increases lung tumor necrosis factor (TNF)-α, interleukin (IL)-10, Toll-like receptor (TLR)-2, TLR-4, and the nuclear factor kappa B (NF-κB) histologically and by RT-qPCR, as well as Immunoglobulin A (IgA) and Immunoglobulin G (IgG) in the bronchoalveolar lavage fluid (BALF), as quantified by ELISA. We also observed an increase in macrophage infiltration and peroxynitrite, a marker of reactive oxygen species (ROS) + reactive nitrogen species (RNS), immunofluorescence staining in the lungs of DEP-exposed and HF-diet animals, which was further exacerbated by concurrent DEP-exposure and HF-diet consumption. Histological examinations revealed enhanced inflammation and collagen deposition in the lungs DEP-exposed mice, regardless of diet. We observed an expansion of Proteobacteria, by qPCR of bacterial 16S rRNA, in the BALF of DEP-exposed mice on the HF diet, which was diminished with probiotic-treatment. Conclusions Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet.

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Section: Discussionsupporting

confidence: 87%

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet

et al. 2021

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“…Numerous researchers have investigated the associations between air pollution and health risk. In our previous study, a DEP-treated murine model and DEP-stimulated AM demonstrated that DEP induce lung in ammation by modulating the NF-kB signaling pathway [21]. However, the molecular mechanisms involved are still not completely understood.…”

Section: Discussionmentioning

confidence: 98%

“…DEP or PM exposure induces cell damage via ROS-mediated oxidative stress [5,21,24]. To determine whether oxidative stress mediates DEP-induced ER stress and in ammatory responses, we evaluated cytotoxicity and reactive oxygen species (ROS) production via MTT assay and DCF-DA uorescence intensity measurement, respectively.…”

Section: Effects Of Cell Viability and Oxidative Stress On Dep Stimulmentioning

confidence: 99%

Diesel exhaust particulates induce neutrophilic lung inflammation by modulating endoplasmic reticulum stress-mediated CXCL1/KC expression in alveolar macrophages

Kim¹,

Song²,

Lee³

2020

Preprint

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Background Exposure to particular matter (PM)2.5, including diesel exhaust particulates (DEP), has adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to respiratory disease pathogenesis such as lung inflammation. However, there is little published research on the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM). Here, we examined ER stress and inflammatory responses in a DEP-induced murine lung inflammation model and in DEP-stimulated AM.Results DEP treatment increased relative lung weight and the number of total cells, neutrophils, and lymphocytes in mouse BALF. Histological examinations also showed that DEP exposure induced neutrophilic lung inflammation and increased the number of DEP-pigmented AM. Western blot analysis showed that BiP and CHOP were relatively upregulated in DEP-induced mouse lung tissues. DEP caused cell damage, increased intracellular reactive oxygen species (ROS), and upregulated the genes associated with inflammation (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, interferon-γ, and toll-like receptor 4) and with ER stress (bound immunoglobulin protein [BiP], CCAAT/enhancer binding protein-homologous protein [CHOP], sXBP-1, and activating transcription factor 4) in AM. Furthermore, DEP stimulation upregulated the gene encoding the chemokine CXCL1/KC in AM.Conclusions DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in alveolar macrophages.

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“…Female Balb/c mice (Orient Bio, Seongnam, Korea) weighing 16.10 ± 0.52 g were housed in a temperature-controlled room ( [22]. During the in vivo experiment, the total amount of exposure is 75, 150, and 300 µg per mouse.…”

Section: Animalsmentioning

confidence: 99%

“…# p < 0.05 or ### p < 0.001 vs. control.2.6. Effects of Cell Cytotoxicity and Oxidative Stress on DEP Stimulation in AMDEP or PM exposure induces cell damage via reactive oxygen species (ROS)-mediated oxidative stress[5,22,23]. To determine whether oxidative stress mediates DEP-induced ER stress and inflammatory responses, we evaluated cytotoxicity and ROS production via 3-(4,5 dimethylthiazol-…”

mentioning

confidence: 99%

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

et al. 2020

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Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.

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TF-343 Alleviates Diesel Exhaust Particulate-Induced Lung Inflammation via Modulation of Nuclear Factor-κB Signaling

Cited by 16 publications

References 56 publications

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet

Diesel exhaust particulates induce neutrophilic lung inflammation by modulating endoplasmic reticulum stress-mediated CXCL1/KC expression in alveolar macrophages

Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

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