PMID: 

Am J Respir Cell Mol Biol. 2011 Feb ;44(2):197-204. Epub 2010 Apr 8. PMID: 20378751

Abstract Title: 

Particulate matter induces translocation of IL-6 from the lung to the systemic circulation.

Abstract: 

The biological mechanisms responsible for an association between elevated concentrations of ambient particulate matter (PM) and increased cardiovascular morbidity and mortality remain unclear. Our laboratory showed that exposure to PM induces systemic inflammation that contributes to vascular dysfunction. This study was designed to determine whether the lung is a major source of systemic inflammatory mediators, using IL-6 as a surrogate marker. We also sought to determine the impact on vascular dysfunction after exposure to PM of less than 10μm in diameter (PM(10)). C57BL/6 mice were intratracheally exposed to a single instillation of PM(10) (10 or 200 μg) or saline. Four hours or 24 hours after exposure, venous and arterial blood samples were simultaneously collected from the right atrium and descending aorta. Concentrations of IL-6were measured in bronchoalveolar lavage fluid (BALF) and serum samples. Vascular functional responses to acetylcholine (ACh) and phenylephrine were measured in the abdominal aorta. Concentrations of IL-6 in BALF samples were increased at 4 and 24 hours after exposure to PM(10). At baseline, concentrations of IL-6 in venous blood were higher than those in arterial blood. Exposure to PM(10) reversed this arteriovenous gradient, 4 hours after exposure. The relaxation responses of the abdominal aorta to ACh decreased 4 hours after exposure to 200 μg PM(10). In IL-6 knockout mice, the instillationof recombinant IL-6 increased IL-6 concentrations in the blood, and exposure to PM(10) did not cause vascular dysfunction. These results support our hypothesis that exposure to PM(10) increases pulmonary inflammatory mediators that translocate to the circulation, contributing to systemic inflammation, with downstream effects such as vascular dysfunction.

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PMID: 

Infect Immun. 2010 Mar ;78(3):1214-20. Epub 2009 Dec 14. PMID: 20008540

Abstract Title: 

Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae.

Abstract: 

Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.

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PMID: 

Chin Med J (Engl). 2018 Oct 20 ;131(20):2461-2473. PMID: 30334531

Abstract Title: 

Fine Particulate Matter-Induced Exacerbation of Allergic Asthma via Activation of T-cell Immunoglobulin and Mucin Domain 1.

Abstract: 

Background: Fine particulate matter (PM) exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PMon the pathology and airway hyperresponsiveness (AHR) of BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA) and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 (TIM-1) in this process.Methods: Forty female BALB/c mice were divided into four groups: control group, OVA group, OVA/PM group, and PM group (n = 10 in each group). Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PMfor 4 h per day and 5 days per week for a total of 8 weeks using a nose-only"PMonline enrichment system"in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PMonline enrichment system only. AHR was detected. Bronchoalveolar lavage fluid (BALF) was collected for cell classification. The levels of interleukin-4 (IL-4), IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs.Results: The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups (P

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PMID: 

J Toxicol Environ Health A. 2017 ;80(4):197-207. Epub 2017 May 11. PMID: 28494199

Abstract Title: 

Fine particulate matter (PM) enhances allergic sensitization in BALB/c mice.

Abstract: 

Ambient particulate matter (PM), a component of air pollution, exacerbates airway inflammation and hyperreactivity in asthmatic patients. Studies showed that PM possesses adjuvant-like properties that enhance the allergic inflammatory response; however, the mechanism (or mechanisms) by which PM enhances the allergic response remains to be determined. The aim of this study was to assess how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway immune response in BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA). Eight-week-old BALB/c male mice were sensitized/challenged with phosphate-buffered saline (PBS/PBS; n = 6), PM/PBS (n = 6), OVA/OVA (n = 6), or OVA + PM/OVA (n = 6). Lung tissue, bronchoalveolar lavage fluid (BALF), and plasma were analyzed for cellular inflammation, cytokines, immunoglobulin E, and heme oxygenase-1 (HO-1) expression. Mice in the OVA + PM/OVA group displayed significantly increased airway inflammation compared to OVA/OVA animals. Total cells, macrophages, and eosinophils recovered in BALF were significantly elevated in the OVA + PM/OVA compared to OVA/OVA group. Histopathological grading indicated that OVA + PM/OVA treatment induced significant inflammation compared to OVA/OVA. Both immunoglobulin (Ig) E and tumor necrosis factor (TNF)α levels were significantly increased in OVA/OVA and OVA + PM /OVA groups compared to PBS/PBS control. The number of HO-1 positive alveolar macrophages was significantly elevated in lungs of mice treated with OVA + PM /OVA compared to OVA/OVA. Our findings suggest that fine PM enhances allergic inflammatory response in pulmonary tissue through mechanisms involving increased oxidative stress.

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PMID: 

Exp Anim. 2019 May 8 ;68(2):159-168. Epub 2018 Dec 10. PMID: 30531117

Abstract Title: 

The acute pulmonary toxicity in mice induced by Staphylococcus aureus, particulate matter, and their combination.

Abstract: 

Inhalation of pathogenic bacteria transported by particulate matter (PM) presents an important potential threat to human health. Therefore, the pulmonary toxicity in mice caused by Staphylococcus aureus (S. aureus) and PM as individual matter and mixtures was studied. PM and S. aureus were instilled intratracheally into Kunming mice at doses of 0.2 mg/mouse and 5.08× 10CFU /mouse, respectively, as individual matter and in combination two times at 5-day intervals. After the exposure period, oxidative stress markers and nitric oxide (NO) in the lung, cellular infiltration, neurotrophins, chemokines, and cytokines in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in sera were examined. Exposure to the combination of PM and S. aureus caused significant increases in malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and NO and significant decreases in total antioxidant capacity (T-AOC) and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in the lung. Meanwhile, the ratio of interleukin (IL)-4 to interferon (INF)-γ, the IL-4 level in BALF, and the IgE concentration in sera were significantly increased in the groups exposed to S. aureus or the combination of PM and S. aureus. Substance P and IL-8 in BALF were significantly increased in mice exposed to PM, S. aureus or their combination. In addition, PM, S. aureus, and their combination caused infiltration of leukocytes into the alveolar tissue spaces. The results suggested that exposure to the combination of PM and S. aureus induced a lung inflammatory response that was at least partly caused by oxidative stress and mediators from the activated eosinophils, neutrophils, alveolar macrophages, and epithelial cells.

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PMID: 

Ecotoxicol Environ Saf. 2018 Nov 15 ;163:612-619. Epub 2018 Aug 6. PMID: 30092543

Abstract Title: 

NLRP3 inflammasome activation and lung fibrosis caused by airborne fine particulate matter.

Abstract: 

Airborne fine particulate matter (PM) has been known capable of causing lung inflammation and fibrosis, as a result of a series of chronic respiration diseases. Although NLRP3 inflammasome activation is essential for development of many chronic diseases, the relationship between PM-induced toxicological effect and NLRP3 inflammasome activation is rarely investigated. Since PMcontains a large population of nanosized materials and many types of nanomaterials can activate NLRP3 inflammasome, the NLRP3 inflammasome activation and lung fibrosis induced by PMwere investigated in the present study. PMwas found capable of causing weak cell death but potent IL-1β secretion in THP-1 cells, which was involved in NLRP3 inflammasome activation as evidenced by Z-YVAD-FMK inhibited IL-1β secretion and overexpressed ASC and NLRP3 protein in PMtreated cells. PMcould be internalized into cells through multiple endocytosis processes, such as phagocytosis and pinocytosis (macropinocytosis, clathrin- and caveolin-mediated endocytosis), and activate NLRP3 inflammasome through cathepsin B release, ROS production, and potassium efflux. After 21 days of exposure to PMthrough oropharyngeal aspiration, Balb/c mice showed increased IL-1β and TGF-β1 levels in the bronchoalveolar lavage fluid (BALF) of lung and significant collagen deposition around small airways of mice, suggesting potential lung inflammation and pulmonary fibrosis.

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PMID: 

Oncotarget. 2017 Nov 17 ;8(58):98567-98579. Epub 2017 Oct 6. PMID: 29228711

Abstract Title: 

At seeming safe concentrations, synergistic effects of PMand formaldehyde co-exposure induces Alzheimer-like changes in mouse brain.

Abstract: 

Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Air pollution is a multi-pollutants co-exposure system, which may affect brain. The indoor environment is where exposure to both air particulate matter (

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PMID: 

Ecotoxicol Environ Saf. 2019 May 15 ;172:33-39. Epub 2019 Jan 19. PMID: 30669072

Abstract Title: 

Vitamin E reduces the extent of mouse brain damage induced by combined exposure to formaldehyde and PM2.5.

Abstract: 

Exposure to specific air pollutants has been demonstrated to induce damage in the brain. However, these studies ignore the effects of a combination of contaminants, and there is a high likelihood that people will be exposed to a mixture of contaminants in daily life. Our previous study showed that co-exposure to formaldehyde (FA) and PM2.5 induced damage in the mouse brain at the safe exposure level for FA or PM2.5 exposure alone, and that oxidative stress and inflammation may be involved in the toxicity mechanisms. A universal strategy to protect people exposed to FA and PM2.5 is urgently needed. To explore whether an exogenous substance could counteract the negative effects of exposure to these pollutants, we administered vitamin E (Vit E) to the experimental animals. The results showed that administration of Vit E in tandem with the FA and PM2.5 co-exposure, reduced the extent of damage to the mouse brain. Down-regulation of oxidative stress and inflammation were proposed to explain the protective effects of Vit E. This research provides a universal strategy to effectively protect people who are exposed to FA and PM2.5 simultaneously.

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PMID: 

Environ Sci Pollut Res Int. 2018 Aug ;25(22):22153-22162. Epub 2018 May 26. PMID: 29804245

Abstract Title: 

The protective effects of selenium supplementation on ambient PMinduced cardiovascular injury in rats.

Abstract: 

Substantial epidemiological and experimental studies have shown that ambient fine particulate matter (PM) exposure can lead to myocardial damage in human and animal through the mechanism of inflammation and oxidative stress. The purpose of the current study was to investigate whether selenium yeast (SeY) supplementation could prevent cardiovascular injury caused by PMin rats. Fifty-six Sprague-Dawley rats were randomly divided into seven groups: saline control group; solvent control group, low-, middle-, and high-dose Se pretreatment groups, PMexposure group, and high-dose Se control group. The rats were pretreated with different concentration of dietary SeY for 28 days, then were exposed to PM.by intratracheal instillation every other day, a total of three times. The levels of inflammatory markers (tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), soluble intercellular adhesion molecule-1 (sICAM-1), and oxidative responses-related indicators total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured in blood and myocardium ofthe left ventricle. The results showed that although PMcaused a decrease of T-AOC, T-AOD, and GSH-Px and increase of MDA and sICM-1, pretreatment with SeY induced a dose-dependent increase in these anti-oxidative indicators and a decrease in oxidative indicators. In addition, the levels of TNF-α and IL-1β in Se pretreatment groups were significantly lower than that in PMexposure group. The results indicated that Se supplementation could effectively prevent cardiovascular inflammation and oxidative stress induced by PM. The results also indicated that the nutritional supplementation might be an effective way to protecting people's health from air pollution.

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PMID: 

Chemosphere. 2017 Apr ;173:14-21. Epub 2017 Jan 8. PMID: 28104476

Abstract Title: 

Combined effects of vitamin E and omega-3 fatty acids on protecting ambient PM-induced cardiovascular injury in rats.

Abstract: 

OBJECTIVE: This study aims to observe whether the combined treatment with vitamin E (vit E) and omega-3 polyunsaturated fatty acids (Ω-3 FA) could prevent the fine particulate matter (PM)-induced cardiovascular injury through alleviating inflammation and oxidative stress. At the same time, the appropriate combination dosage of vit E andΩ-3 FA was explored to find an optimized protective dose to protect the injury induced by PM.METHODS: The SD rats were pretreated with different concentration of vit E andΩ-3 FA separately or jointly. Then the rats were exposed to ambient PMby intratracheal instillation for three times. The expression of tumor necrosis factorα (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in serum and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde (MDA), superoxide Dismutase (SOD) and glutathione-peroxidase (GSH-Px) in myocardium and the level of MDA in serum were measured. Meanwhile, the cardiac injury was evaluated by histopathological examination.RESULTS: Compared with the severe injury of rats in PMexposure group, the rats in vit E orΩ-3 FA-pretreated groups had a slighter injury in heart. Meanwhile, pretreatment with vit E or Ω-3 FA induced a significantly alleviation of the inflammatory cytokines (TNF-α, IL-1β, IL-6) and the elevation of the anti-oxidative activity especially in the rats pretreated with combined vit E andΩ-3 FA. In addition, the combined protecting effects of vit E and Ω-3 FA showed a dose-dependent manner.CONCLUSION: Supplementation with vit E andΩ-3 FA could protect the PM-induced injury, and the combination of vit E andΩ-3 FA might produce more effective effects than the separate nutrient did.

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