Acute Exposure to Diesel-Biodiesel Particulate Matter Promotes Murine Lung Oxidative Stress by Nrf2/HO-1 and Inflammation Through the NF-kB/TNF-α Pathways

Cattani‐Cavalieri, Isabella; Lanzetti, Manuella; Carvalho, Giovanna; Zin, Walter A.; Monte‐Alto‐Costa, Andréa; Pôrto, Luís Cristóvão; Romana‐Souza, Bruna

doi:10.1007/s10753-018-0910-8

Cited by 28 publications

(30 citation statements)

References 23 publications

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“…To our surprise, DEP exposure, either with or without DMF treatment, did not affect Nrf2 protein levels. In contrast, our recent study demonstrated an elevation of Nrf2 expression after a 5-day exposure of mice to biodiesel particulate matter, albeit with a much higher dose (250 µg) than used in the present study [25]. Interestingly, we did observe an elevation in Keap-1 protein levels after chronic DEP exposure, which could be reduced to basal levels by DMF treatment (Figure 3).…”

Section: Discussioncontrasting

confidence: 94%

“…Exposure of mice to DEP from the vent of a workshop in a diesel engine manufacturing factory by intratracheal instillation increased the expression of both Nrf2 gene and Nrf2 protein in the lung measured up to 48 h after exposure to DEP [24]. Recently, our group demonstrated that mice exposed to biodiesel particulate matter elevated Nrf2 protein expression in the lung after 5-day exposure to the pollutant [25].…”

Section: Introductionmentioning

confidence: 94%

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Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice

Cattani‐Cavalieri

Valença

Moraes

et al. 2020

IJMS

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Air pollution is mainly caused by burning of fossil fuels, such as diesel, and is associated with increased morbidity and mortality due to adverse health effects induced by inflammation and oxidative stress. Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an antioxidant and anti-inflammatory agent. We investigated the potential therapeutic effects of DMF on pulmonary damage caused by chronic exposure to diesel exhaust particles (DEPs). Mice were challenged with DEPs (30 μg per mice) by intranasal instillation for 60 consecutive days. After the first 30 days, the animals were treated daily with 30 mg/kg of DMF by gavage for the remainder of the experimental period. We demonstrated a reduction in total inflammatory cell number in the bronchoalveolar lavage (BAL) of mice subjected to DEP + DMF as compared to those exposed to DEPs alone. Importantly, DMF treatment was able to reduce lung injury caused by DEP exposure. Intracellular total reactive oxygen species (ROS), peroxynitrite (OONO), and nitric oxide (NO) levels were significantly lower in the DEP + DMF than in the DEP group. In addition, DMF treatment reduced the protein expression of kelch-like ECH-associated protein 1 (Keap-1) in lung lysates from DEP-exposed mice, whereas total nuclear factor κB (NF-κB) p65 expression was decreased below baseline in the DEP + DMF group compared to both the control and DEP groups. Lastly, DMF markedly reduced DEP-induced expression of nitrotyrosine, glutathione peroxidase-1/2 (Gpx-1/2), and catalase in mouse lungs. In summary, DMF treatment effectively reduced lung injury, inflammation, and oxidative and nitrosative stress induced by chronic DEP exposure. Consequently, it may lead to new therapies to diminish lung injury caused by air pollutants.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice

Cattani‐Cavalieri

Valença

Moraes

et al. 2020

IJMS

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“…GM-CSF regulates the clearance or catabolism rather than synthesis of surfactant proteins and lipids. It has been reported that respiratory epithelial cells synthesize GM-CSF, which is consistent with the hypothesis that GM-CSF plays an important role in surfactant metabolism [ 30 ]. In our study, GM-CSF levels in lung tissues increased markedly after DE exposure in Nrf2 +/+ mice but decreased markedly after DE exposure in Nrf2 −/− mice.…”

Section: Discussionsupporting

confidence: 87%

“…A recent study suggests that biodiesel (DB) particulate matter by intranasal instillation promotes oxidative stress by activating the Nrf2/HO-1 and inflammation by p-NF-kB/TNF-α pathways. The protein expression levels of Nrf2, p-NF-kB, and HO-1 were higher in the low-dose DB (250 μg) group and lower in the high-dose DB (1000 μg) group than in control mice and the low-dose DB group [ 30 ]. It also has been reported that the TNF-α secretion by alveolar macrophages was reduced after high-dose DE exposure (3 mg/m 3 ) in mice [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice

Shimizu

Shinkai

et al. 2020

Biomedicines

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In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2−/− mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in Nrf2−/− mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2−/− mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2−/− mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2−/− mice after DE exposure. Our results suggested that Nrf2 reduces the risk of pulmonary disease via modulating the airway innate immune response caused by DE in mice.

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“…Overexpression or knockdown of miR-181a-5p resulted in an up-regulation or down-regulation in the expression of TLR-2, MYD88 and pro-in ammatory cytokines (IL-1β and TNF-α). NF-κB acts at the center of the in ammatory response and controls the gene expression of numerous in ammation-associated substances, including IL-1β, IL-6, IL-8, and TNF-α, which induce a cascade of in ammatory responses and related lung damage [41][42][43][44]. Several researches reported that MG activates IL-1β production through the NF-κB pathway via TLR2 and MyD88.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-181a-5p Protects against MG Infection by Targeting PPM1B and Activating the TLR2-Mediated MyD88/NF-κB Pathway

Sun¹,

Zhao²,

Pang³

et al. 2020

Preprint

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BackgroundMycoplasma gallisepticum (MG) is one of the most important pathogens that causes chronic respiratory disease (CRD) in chickens. Exosomes secreted from cells have been well documented to deliver miRNAs to recipient cells to modulate cellular function. The purpose of this current study was to explore the functions of exosomal miR-181a-5p in MG infection and the underlying mechanisms. ResultsHere, we found that miR-181a-5p expression in vivo and in vitro was significantly upregulated after MG infection. Exosomes enriched in MG-infected chicken type-II pneumocytes (CP-II) could selectively load miR-181a-5p and transfer it into recipient DF-1 cells. PPM1B was further identified as the target gene of miR-181a-5p. Overexpression of miR-181a-5p and/or knockdown of PPM1B activated the TLR2-mediated MyD88/NF-κB signaling pathways, whereas inhibition of miR-181a-5p and the overexpression of PPM1B led to the opposite results. In addition, depressing miR-181a-5p significantly reduced the expression of tumor necrosis factors alpha (TNF-α) and interleukin-1β (IL-1β) by MG-induced. Upregulated miR-181a-5p promoted cell proliferation and cell cycle progression and inhibited apoptosis to resist MG infection. Moreover, overexpression of miR-181a-5p significantly depressed pMAG1.2 expression by directly inhibiting PPM1B.ConclusionsTaken together, we conclude that the newly identified primary CP-II cells exosomal miR-181a-5p activates the TLR2-mediated MyD88/NF-κB pathway by directly targeting PPM1B to promote pro-inflammatory cytokines expression for defending against MG infection in recipient DF-1 cells.

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Acute Exposure to Diesel-Biodiesel Particulate Matter Promotes Murine Lung Oxidative Stress by Nrf2/HO-1 and Inflammation Through the NF-kB/TNF-α Pathways

Cited by 28 publications

References 23 publications

Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice

Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice

Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice

Exosomal miR-181a-5p Protects against MG Infection by Targeting PPM1B and Activating the TLR2-Mediated MyD88/NF-κB Pathway

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