The presence of microplastics in the various food web raised concerns on human health, but little is known about the target cells and mechanism of toxicity of microplastics. In this study, we evaluated the toxicity of microplastics using relevant cell lines to the oral route of exposure. Approximately 100 μm-sized fragment-type polypropylene (PP) and polystyrene (PS) particles were prepared by sieving after pulverization and further applied the accelerated weathering using ultraviolet and heat. Thus, the panel of microplastics includes fresh PP (f-PP), fresh PS (f-PS), weathered PP (w-PP), and weathered PS (w-PS). The spherical PS with a similar size was used as a reference particle. Treatment of all types of PP and PS did not show any toxic effects to the Caco-2 cells and HepG2 cells. However, the treatment of microplastics to THP-1 macrophages showed significant toxicity in the order of f-PS > f-PP > w-PS > w-PP. The weathering process significantly reduced the reactive oxygen species (ROS) generation potential of both microplastics because the weathered microplastics have an increased affinity to bind serum protein which acts as a ROS scavenger. The intrinsic ROS generation potential of microplastics showed a good correlation with the toxicity endpoints including cytotoxicity and pro-inflammatory cytokines in THP-1 macrophages. In conclusion, the results of this study suggest that the target cell type of microplastics via oral administration can be macrophages and the pathogenic factor to THP-1 macrophages is the intrinsic ROS generation potential of microplastics. Nevertheless, the toxic effect of microplastics tested in this study was much less than that of nano-sized particles.

Environmentally persistent free radicals (EPFRs) are easily generated in the combustion processes of municipal solid waste (MSW) and can cause adverse effects on human health. This study focuses on understanding the toxicity of EPFR particles (ZnO/MCB containing EPFRs) to human bronchial epithelial cell lines BEAS-2B and 16HBE, murine macrophages Raw264.7, and the lung of BALB/c mice after a short exposure (7 days). Exposure of BEAS-2B, 16HBE, and Raw264.7 cells to ZnO/MCB particles significantly increased the reactive oxygen species (ROS) production and perturbed levels of intracellular redox conditions (decreased the intracellular GSH level and the activity of cytosolic SOD, and stimulated oxidative stress related proteins such as HO-1 and Nrf2). EPFR particles decreased the mitochondrial membrane potential (MMP) and induced cell apoptosis, including the activation of Caspase-3, Bax, and Bcl-2 apoptotic signalling pathways. A signature inflammatory condition was observed in both cell models and the mouse model for lung lesions. Our data suggest that EPFRs in particles have greater toxicity to lung cells and tissues that are potential health hazards to human lung.

Exposure to fine atmospheric Particulate Matter (PM) is one of the major environmental causes involved in the development of inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD) or asthma. When PM is penetrating in the pulmonary system, alveolar macrophages represent the first line of defense, in particular by triggering a pro-inflammatory response, and also by their ability to recruit infiltrating macrophages from the bone marrow. The aim of this in vitro study was to evaluate the gene expression and cytokine production involved in the toxicological and inflammatory responses of infiltrating macrophages, as well as the Extracellular Vesicles (EVs) production, after their exposure to PM. The ability of these EVs to convey information related to PM exposure from exposed macrophages to pulmonary epithelial cells was also evaluated.Infiltrating macrophages respond to fine particles exposure in a conventional manner, as their exposure to PM induced the expression of Xenobiotic Metabolizing Enzymes (XMEs) such as CYP1A1 and CYP1B1, the enzymes involved in oxidative stress SOD2, NQO1 and HMOX as well as pro-inflammatory cytokines in a dose-dependent manner. Exposure to PM also induced a greater release of EVs in a dose-dependent manner. In addition, the produced EVs were able to induce a pro-inflammatory phenotype on pulmonary epithelial cells, with the induction of the release of IL6 and TNFα proinflammatory cytokines. These results suggest that infiltrating macrophages participate in the pro-inflammatory response induced by PM exposure and that EVs could be involved in this mechanism.

Ambient particulate matter (PM) exposure is associated with pulmonary and cardiovascular diseases; however, there is scant research linking data on animal and human cells. The objective of this study was to investigate these associations. Vascular remodeling plays a crucial role in both pulmonary and cardiovascular diseases. Therefore, we conducted a transcriptomic analysis using vascular smooth muscle cells (VSMCs) to identify potential regulators or markers of PM exposure. We demonstrated that fine and coarse PM increased VSMC proliferation in mice. We conducted a genome-wide cDNA microarray analysis, followed by a pathway analysis of VSMCs treated with coarse PM for durations of 24, 48, and 72 h. Sixteen genes were discovered to be time-dependently upregulated and involved in VSMC proliferation. Osteopontin (OPN) is indicated as one of the regulators of these upregulated genes. Both fine and coarse PM from industrial and urban areas significantly increased OPN expression in VSMCs and macrophages. Moreover, oropharyngeal instillation of fine and coarse PM for 8 weeks increased the VSMCs in the pulmonary arteries of mice. OPN level was consistently increased in the lung tissues, bronchoalveolar lavage fluid, and serum of mice. Moreover, we analyzed the plasma OPN levels of 72 healthy participants recruited from the studied metropolitan area. Each participant wore a personal PM2.5 sampler to assess their PM2.5 exposure over a 24 h period. Our results indicate that personal exposure to fine PM is positively correlated with plasma OPN level in young adults. The data obtained in this study suggest that exposure to fine and coarse PM may cause pulmonary vascular lesions in humans and that OPN level may be a biomarker of PM exposure in humans.

Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles.The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions.Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects.After 6 h exposure, no genes or proteins for oxidative stress or pro-inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure.The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures.

The primary objective of the present study was to review the impact of Cd exposure on gut microbiota and intestinal physiology, as well as to estimate whether gut may be considered as the target for Cd toxicity. The review is based on literature search in available databases. The existing data demonstrate that the impact of Cd on gut physiology is two-sided. First, Cd exposure induces a significant alteration of bacterial populations and their relative abundance in gut (increased Bacteroidetes-to-Firmicutes ratio), accompanied by increased lipopolysaccharide (LPS) production, reflecting changed metabolic activity of the intestinal microbiome. Second, in intestinal wall Cd exposure induces inflammatory response and cell damage including disruption of tight junctions, ultimately leading to increased gut permeability. Together with increased LPS production, impaired barrier function causes endotoxinemia and systemic inflammation. Hypothetically, Cd-induced increase gut permeability may also result in increased bacterial translocation. On the one hand, bacteriolysis may be associated with aggravation of endotoxemia. At the same time, together with Cd-induced impairment of macrophage inflammatory response, increased bacterial translocation may result in increased susceptibility to infections. Such a supposition is generally in agreement with the finding of higher susceptibility of Cd-exposed mice to infections. The changed microbiome metabolic activity and LPS-induced systemic inflammation may have a significant impact on target organs. The efficiency of probiotics in at least partial prevention of the local (intestinal) and systemic toxic effects of cadmium confirms the role of altered gut physiology in Cd toxicity. Therefore, probiotic treatment may be considered as the one of the strategies for prevention of Cd toxicity in parallel with chelation, antioxidant, and anti-inflammatory therapy.

This study investigated the effects of particle-bound polycyclic aromatic hydrocarbons (PAHs) produced from burning three incense types on and their bioreactivity in the RAW 264.7 murine macrophage cell line. Gas chromatography/mass spectrometry was used to determine the levels of 16 identified PAHs. Macrophages were exposed to incense particle extracts at concentrations of 0, 3.125, 6.25, 12.5, 25, 50, and 100 μg/mL for 24 h. After exposure, cell viability and nitric oxide (NO) and inflammatory mediator [tumor necrosis factor (TNF)-α] production of the cells were examined. The mean atomic hydrogen (H) to carbon (C) ratios in the environmentally friendly, binchotan charcoal, and lao shan incenses were 0.69, 1.13, and 1.71, respectively. PAH and total toxic equivalent (TEQ) mass fraction in the incenses ranged from 137.84 to 231.00 and 6.73–26.30 pg/μg, respectively. The exposure of RAW 264.7 macrophages to incense particles significantly increased TNF-α and NO production and reduced cell viability. The cells treated with particles collected from smoldering the environmentally friendly incense produced more NO and TNF-α compared to other incenses. Additionally, the TEQ of fluoranthene (FL), pyrene (Pyr), benzo[a]anthracene (BaA), chrysene (Chr), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), indeno[1,2,3-cd]pyrene (INP), dibenz[a,h]anthracene (DBA), and benzo[g,h,i]perylene [B(ghi)P] had a significant correlation (R2 = 0.64–0.98, P < 0.05) with NO and TNF-α production. The current findings indicate that incense particle-bound PAHs are biologically active and that burning an incense with a lower H/C ratio caused higher bioreactivity. The stimulatory effect of PAH-containing particles on molecular mechanisms of inflammation are critical for future study.

The formaldehyde (FA) is a crosslinking agent that reacts with cellular macromolecules such as proteins, nucleic acids and molecules with low molecular weight such as amino acids, and it has been linked to inflammatory processes and oxidative stress. This study aimed to analyze the oxidative effects on pulmonary inflammatory response in Fischer rats exposed to different concentrations of FA. Twenty-eight Fischer rats were divided into 4 groups (N = 7). The control group (CG) was exposed to ambient air and three groups were exposed to different concentrations of FA: 1% (FA1%), 5% (FA5%) and 10% (FA10%). In the Bronchoalveolar Lavage Fluid (BALF), the exposure to a concentration of 10% promoted the increase of inflammatory cells compared to CG. There was also an increase of macrophages and lymphocytes in FA10% and lymphocytes in FA5% compared to CG. The activity of NADPH oxidase in the blood had been higher in FA5% and FA10% compared to CG. The activity of superoxide dismutase enzyme (SOD) had an increase in FA5% and the activity of the catalase enzyme (CAT) showed an increase in FA1% compared to CG. As for the glutathione system, there was an increase in total glutathione (tGSH), reduced glutathione (GSH) and oxidized glutathione (GSSG) in FA5% compared to CG. The reduced/oxidized glutathione ratio (GSH/GSSG) had a decrease in FA5% compared to CG. There was an increase in lipid peroxidation compared to all groups and the protein carbonyl formation in FA10% compared to CG. We also observed an increase in CCL2 and CCL5 chemokines in the treatment groups compared to CG and in serum there was an increase in CCL2, CCL3 and CCL5 compared to CG. Our results point out to the potential of formaldehyde in promoting airway injury by increasing the inflammatory process as well as by the redox imbalance.

Currently, urbanization is associated with an increase in air pollutants that contribute to invasive pathogen infections by altering the host's innate immunity and antimicrobial resistance capability. Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is a gram-positive opportunistic pathogen that causes a wide range of diseases, especially in children and immunosuppressed individuals. Diesel exhaust particle (DEP), a significant constituent of particulate matter (PM), are considered a prominent risk factor for respiratory illness and circulatory diseases worldwide. Several clinical and epidemiological studies have identified a close association between PM and the prevalence of viral and bacterial infections. This study investigated the role of DEP exposure in increasing pulmonary and blood bacterial counts and mortality during GAS M1 strain infection in mice. Thus, we characterized the upregulation of reactive oxygen species production and disruption of tight junctions in the A549 lung epithelial cell line due to DEP exposure, leading to the upregulation of GAS adhesion and invasion. Furthermore, DEP exposure altered the leukocyte components of infiltrated cells in bronchoalveolar lavage fluid, as determined by Diff-Quik staining. The results highlighted the DEP-related macrophage dysfunction, neutrophil impairment, and imbalance in pro-inflammatory cytokine production via the toll-like receptor 4/mitogen-activated protein kinase signaling axis. Notably, the tolerance of the GAS biofilms toward potent antibiotics and bacterial resistance against environmental stresses was also significantly enhanced by DEP. This study aimed to provide a better understanding of the physiological and molecular interactions between exposure to invasive air pollutants and susceptibility to invasive GAS infections.