Biological Influence of Pulmonary Disease Conditions Induced by Particulate Matter on Microfluidic Lung Chips
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ABSTRACT: Supplementary Information
The online version contains supplementary material available at 10.1007/s13206-022-00068-x.
SUBMITTER: Jabbar F
PROVIDER: S-EPMC9263805 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fine particulate matter (PM2.5) released during the livestock industry endangers the respiratory health of animals. Our previous findings suggested that broilers exposed to PM2.5 exhibited lung inflammation and changes in the pulmonary microbiome. Therefore, this study was to investigate whether the pulmonary microbiota plays a causal role in the pathogenesis of PM2.5-induced lung inflammation. We first used antibiotics to establish a pulmonary microbiota intervention broiler model, which showed a significantly reduced total bacterial load in the lungs without affecting the microbiota composition or structure. Based on it, 45 AA broilers of similar body weight were randomly assigned to three groups: control (CON), PM2.5 (PM), and pulmonary microbiota intervention (ABX-PM). From 21 d of age, broilers in the ABX-PM group were intratracheally instilled with antibiotics once a day for 3 d. Meanwhile, broilers in the other two groups were simultaneously instilled with sterile saline. On 24 and 26 d of age, broilers in the PM and ABX-PM groups were intratracheally instilled with PM2.5 suspension to induce lung inflammation, and broilers in the CON group were simultaneously instilled with sterile saline. The lung histomorphology, inflammatory cytokines' expression levels, lung microbiome, and microbial growth conditions were analyzed to determine the effect of the pulmonary microbiota on PM2.5-induced lung inflammation. Broilers in the PM group showed lung histological injury, while broilers in the ABX-PM group had normal lung histomorphology. Furthermore, microbiota intervention significantly reduced mRNA expression levels of interleukin-1β, tumor necrosis factor-α, interleukin-6, interleukin-8, toll-like receptor 4 and nuclear factor kappa-B. PM2.5 induced significant changes in the β diversity and structure of the pulmonary microbiota in the PM group. However, no significant changes in microbiota structure were observed in the ABX-PM group. Moreover, the relative abundance of Enterococcus cecorum in the PM group was significantly higher than that in the CON and ABX-PM groups. And sterile bronchoalveolar lavage fluid from the PM group significantly promoted the growth of E. cecorum, indicating that PM2.5 altered the microbiota's growth condition. In conclusion, pulmonary microbiota can affect PM2.5-induced lung inflammation in broilers. PM2.5 can alter the bacterial growth environment and promote dysbiosis, potentially exacerbating inflammation.
| S-EPMC10390102 | biostudies-literature
Project description:Exposure to fine particulate matter (PM) with aerodynamic diameter ?2.5 ?m (PM2. 5) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. As reported recently, PM2. 5 exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM2. 5 alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM2. 5 exposure combined with Streptococcus pneumonia infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3-V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher's diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM2. 5 or pneumococcus when compared with the control group. The genera Streptococcus, Prevotella, Leptotrichia, and Granulicatella were remarkably increased in mice exposed to PM2. 5 combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM2. 5 and pneumococcus than that in mouse groups exposed to either PM2. 5 or pneumococcal infection alone. Our results demonstrate that PM2. 5 alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis.
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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression
2007-12-01 | GSE9465 | GEO
Project description:Air pollution is a ubiquitous problem and comprises gaseous and particulate matter (PM). Epidemiological studies have clearly shown that exposure to PM is associated with impaired lung function and the development of lung diseases, such as chronic obstructive pulmonary disease and asthma. To understand the mechanisms involved, animal models are often used. However, the majority of such models represent high levels of exposure and are not representative of the exposure levels in less polluted countries, such as Australia. Therefore, in this study, we aimed to determine whether low dose PM10 exposure has any detrimental effect on the lungs. Mice were intranasally exposed to saline or traffic-related PM10 (1?g or 5?g/day) for 3 wk. Bronchoalveolar lavage (BAL) and lung tissue were analyzed. PM10 at 1 ?g did not significantly affect inflammatory and mitochondrial markers. At 5 ?g, PM10 exposure increased lymphocytes and macrophages in BAL fluid. Increased NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and IL-1? production occurred following PM10 exposure. PM10 (5 ?g) exposure reduced mitochondrial antioxidant manganese superoxide (antioxidant defense system) and mitochondrial fusion marker (OPA-1), while it increased fission marker (Drp-1). Autophagy marker light-chain 3 microtubule-associated protein (LC3)-II and phosphorylated-AMPK were reduced, and apoptosis marker (caspase 3) was increased. No significant change of remodeling markers was observed. In conclusion, a subchronic low-level exposure to PM can have an adverse effect on lung health, which should be taken into consideration for the planning of roads and residential buildings.
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Project description:Particulate matter with a diameter ≤2.5 µm (PM2.5) has a complex composition and has been associated with the incidence of cardiopulmonary disease and premature death in humans. However, whether pure particulate fractions of PM2.5 (PPP2.5), which are composed primarily of carbon, are responsible for the toxicity caused by ambient particulate matter (original PM2.5 particles, OPP2.5) is currently unclear. The present study assessed the acute toxic effects of OPP2.5 sampled in Beijing, China and of its PPP2.5 fraction in male BALB/c mice. The mice were intratracheally instilled with a single dose of aerosolized OPP2.5 or PPP2.5. Blood, lungs and bronchoalveolar lavage fluid were collected after 24 h for histopathology, flow cytometry and the measurement of pro-inflammatory cytokines/chemokines and other biochemical factors. Both OPP2.5 and PPP2.5 caused acute toxicity, particularly inflammatory responses, including an increase in the levels of pro-inflammatory cytokines and an accumulation of numerous immune cells in the lungs. OPP2.5 induced a stronger inflammatory response than PPP2.5. The complex components adsorbed into the solid core granules of OPP2.5 and the granules themselves contributed to the toxic effects.
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Project description:Particulate matter (PM) is a huge environmental threat of public concern. Oxidative stress and systemic inflammation are the known factors contributing to PM related damage; however, a systematic understanding of the PM-induced deleterious pulmonary effects is still not clear. Thus, we performed multi-omics analysis in a mouse model of 3-month PM exposure to identify molecular changes in the lung tissues.
2022-01-11 | PXD030874 |
Project description:Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.
2023-05-31 | GSE217456 | GEO
Project description:Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations.We investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 mum) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures.We exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice.Consistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (T(H)1) cytokines [interferon-gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha] and T(H)2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways.This study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics.
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Project description:BackgroundCaloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.ResultsMale C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.ConclusionThese novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.
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Project description:Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time.
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