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The knowledge of the underlying mechanisms by which particulate matter (PM) exerts its health effects is still incomplete since it may trigger various symptoms as some persons may be more susceptible than others. Detailed studies realized in more relevant in vitro models are highly needed. Healthy normal human bronchial epithelial (NHBE), asthma-diseased human bronchial epithelial (DHBE), and COPD-DHBE cells, differentiated at the air-liquid interface, were acutely or repeatedly exposed to fine (i.e., PM 2.5-0.18 , also called FP) and quasi-ultrafine (i.e., PM 0.18 , also called UFP) particles. Immunofluorescence labelling of pan-cytokeratin, MUC5AC, and ZO-1 confirmed their specific cell-types. Baselines of the inflammatory mediators secreted by all the cells were quite similar. Slight changes of TNFα, IL-1β, IL-6, IL-8, GM-CSF, MCP-1, and/or TGFα, and of H3K9 histone acetylation supported a higher inflammatory response of asthma- and especially COPD-DHBE cells, after exposure to FP and especially UFP. At baseline, 35 differentially expressed genes (DEG) in asthma-DHBE, and 23 DEG in COPD-DHBE, compared to NHBE cells, were reported. They were involved in biological processes implicated in the development of asthma and COPD diseases, such as cellular process (e.g., PLA2G4C, NLRP1, S100A5, MUC1), biological regulation (e.g., CCNE1), developmental process (e.g., WNT10B), and cell component organization and synthesis (e.g., KRT34, COL6A1, COL6A2). In all the FP or UFP-exposed cell models, DEG were also functionally annotated to the chemical metabolic process (e.g., CYP1A1, CYP1B1, CYP1A2) and inflammatory response (e.g., EREG). Another DEG, FGF-1, was only down-regulated in asthma and specially COPD-DHBE cells repeatedly exposed. While RAB37 could help to counteract the down-regulation of FGF-1 in asthma-DHBE cells, the deregulation of FGR, WNT7B, VIPR1, and PPARGC1A could dramatically contribute to make it worse in COPD-DHBE cells. Taken together, these data contributed to support the highest effects of UFP versus FP and highest sensitivity of asthma- and notably COPD-DHBE versus NHBE cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A particular attention has been devoted to the type of toxicological responses induced by particulate matter (PM), since their knowledge is greatly complicated by the fact that it is a heterogeneous and often poorly described pollutant. However, despite intensive research effort, there is still a lack of knowledge about the specific chemical fraction of PM, which could be mainly responsible of its adverse health effects. We sought also to better investigate the toxicological effects of organic extractable matter (OEM) in normal human bronchial epithelial lung BEAS-2B cells. The wide variety of chemicals, including PAH and other related-chemicals, found in OEM, has been rather associated with early oxidative events, as supported by the early activation of the sensible NRF-2 signaling pathway. For the most harmful conditions, the activation of this signaling pathway could not totally counteract the ROS overproduction, thereby leading to critical oxidative damage to macromolecules (lipid peroxidation, oxidative DNA adducts). While NRF-2 is an anti-inflammatory, OEM exposure did not trigger any significant change in the secretion of inflammatory cytokines (i.e., TNFα, IL-1β, IL-6, IL-8, MCP-1, and IFNγ). According to the high concentrations of PAH and other related organic chemicals found in this OEM, CYP1A1 and 1B1 genes exhibited high transcription levels in BEAS-2B cells, thereby supporting both the activation of the critical AhR signaling pathway and the formation of highly reactive ultimate metabolites. As a consequence, genotoxic events occurred in BEAS-2B cells exposed to this OEM together with cell survival events, with possible harmful cell cycle deregulation. However, more studies are required to implement these observations and to contribute to better decipher the critical role of the organic fraction of air pollution-derived PM 2.5 in the activation of some sensitive signaling pathways closely associated with G1/S and intra-S checkpoint blockage, on the one hand, and cell survival, on the other hand., (Copyright © 2019 Elsevier Inc. All rights reserved.)

According to the literature, tiny amounts of transition metals in airborne fine particles (PM 2.5 ) may induce proinflammatory cell response through reactive oxygen species production. The solubility of particle-bound metals in physiological fluids, i.e. the metal bioaccessibility is driven by factors such as the solution chemical composition, the contact time with the particles, and the solid-to-liquid phase ratio (S/L). In this work, PM 2.5 -bound metal bioaccessibility was assessed in various physiological-like solutions including cell culture media in order to evidence the potential impact on normal human bronchial epithelial cells (NHBE) when studying the cytotoxicity and inflammatory responses of PM 2.5 towards the target bronchial compartment. Different fluids (H 2 O, PBS, LHC-9 culture medium, Gamble and human respiratory mucus collected from COPD patients), various S/L conditions (from 1/6000 to 1/100,000) and exposure times (6, 24 and 72h) were tested on urban PM 2.5 samples. In addition, metals' total, soluble and insoluble fractions from PM 2.5 in LHC-9 were deposited on NHBE cells (BEAS-2B) to measure their cytotoxicity and inflammatory potential (i.e., G6PDH activity, secretion of IL-6 and IL-8). The bioaccessibility is solution-dependent. A higher salinity or organic content may increase or inhibit the bioaccessibiliy according to the element, as observed in the complex mucus matrix. Decreasing the S/L ratio also affect the bioaccessibility depending on the solution tested while the exposure time appears less critical. The LHC-9 culture medium appears to be a good physiological proxy as it induces metal bioaccessibilities close to the mucus values and is little affected by S/L ratios or exposure time. Only the insoluble fraction can be linked to the PM 2.5 -induced cytotoxicity. By contrast, both soluble and insoluble fractions can be related to the secretion of cytokines. The metal bioaccessibility in LHC-9 of the total, soluble, and insoluble fractions of the PM 2.5 under study did not explain alone, the cytotoxicity nor the inflammatory response observed in BEAS-2B cells. These findings confirm the urgent need to perform further toxicological studies to better evaluate the synergistic effect of both bioaccessible particle-bound metals and organic species., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM2.5-0.3-exposed coculture model. PM2.5-0.3 exposure of human AM from the coculture model induced marked cell cycle alterations after 24h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM2.5-0.3 was reported in the L132 cells. Exposure of human AM from the coculture model to PM2.5-0.3 resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM2.5-0.3 induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability., (Copyright © 2016 Elsevier Inc. All rights reserved.)

While the evidence for the health adverse effects of air pollution Particulate Matter (PM) has been growing, there is still uncertainty as to which constituents within PM are most harmful. Hence, to contribute to fulfill this gap of knowledge, some physicochemical characteristics and toxicological endpoints (i.e. cytotoxicity, oxidative damage, cytokine secretion) of PM2.5-0.3 samples produced during two different seasons (i.e. spring/summer or autumn/winter) in three different surroundings (i.e. rural, urban, or industrial) were studied, thereby expecting to differentiate their respective adverse effects in human bronchial epithelial cells (BEAS-2B). Physicochemical characteristics were closely related to respective origins and seasons of the six PM2.5-0.3 samples, highlighting the respective contributions of industrial and heavy motor vehicle traffic sources. Space- and season-dependent differences in cytotoxicity of the six PM2.5-0.3 samples could only be supported by considering both the physicochemical properties and the variance in air PM concentrations. Whatever spaces and seasons, dose- and even time-dependent increases in oxidative damage and cytokine secretion were reported in PM2.5-0.3-exposed BEAS-2B cells. However, the relationship between the chemical composition of each of the six PM2.5-0.3 samples and their oxidative or inflammatory potentials seemed to be very complex. These results supported the role of inorganic, ionic and organic components as exogenous source of Reactive Oxygen Species and, thereafter, cytokine secretion. Nevertheless, one of the most striking observation was that some inorganic, ionic and organic chemical components were preferentially associated with early oxidative events whereas others in the later oxidative damage and/or cytokine secretion. Taken together, these results indicated that PM mass concentration alone might not be able to explain the health outcomes, because PM is chemically nonspecific, and supported growing evidence that PM-size, composition and emission source, together with sampling season, interact in a complex manner to produce PM2.5-0.3-induced human adverse health effects., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The massive increase in emissions of air pollutants due to economic and industrial growth in developing countries has made air quality a crucial health problem in this continent. Hence, it is somewhat critical to have a better knowledge on the air pollution in Sub-Saharan Africa countries. Three air pollution PM2.5 samples were also collected in two urban sites (i.e., Fann and Faidherbe) in Dakar (Senegal) and in a rural site near Dakar (i.e., Ngaparu). The two urban sites mainly differ in the type of used vehicles: in Fann, most of the traffic is made of buses, which are absent, in Faidherbe. The physicochemical characteristics of the three PM2.5 samples revealed their high heterogeneities and complexities, related to the multiple natural and anthropogenic emission sources. Results from 5-bromodeoxyuridine incorporation into DNA, mitochondrial dehydrogenase activity, and extracellular lactate dehydrogenase activity in PM2.5-exposed BEAS-2B cells suggested the exposure conditions (i.e., 3 and 12 μg PM/cm² during 24, 48, and 72 h) to further consider. The organic fractions (i.e., mainly PAHs) of the PM(2.5) samples were able to induce a time and/or concentration-dependent gene expression of CYP1A1 and CYP1B1, and, to a lesser extent, NQO1. There was a time and/or dose-dependent increase of both the gene expression and/or protein secretion of inflammatory mediators (i.e., TNF-α, IL-1β, IL-6, and/or IL-8) in PM(2.5)-exposed BEAS-2B cells. In agreement with the physicochemical characterization, urban PM(2.5) samples caused greater biological responses in BEAS-2B cells than the rural one. Variable concentrations of transition metals (i.e., Fe, Al, Pb, Mn, Zn) and organic compounds (i.e., PAHs) founded in the three PM2.5 samples might be firmly involved in a time- and/or dose-dependent toxicity, relying on inflammatory processes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

To contribute to complete the knowledge of the underlying mechanisms of action involved in air pollution particulate matter (PM)-induced cytotoxicity, an aerosol was collected in Dunkerque, a French seaside City heavily industrialized. In this work, we focused our attention on its physical and chemical characteristics, its cytotoxicity, and its role in the induction of the volatile organic compound (VOC) and/or polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes in human lung epithelial cells (A549). Size distribution showed that 92.15% of the collected PM were PM2.5 and the specific surface area was 1 m2/g. Inorganic (i.e. Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. VOC, PAH, etc.) chemicals were found in collected PM, revealing that much of them derived from wind-borne dust from the industrial complex and the heavy motor vehicle traffic. The thermal desorption study indicated that organic chemicals were not only adsorbed onto the surface but also highly incrusted in the structure of PM. The lethal concentrations at 10% and 50% of collected PM were 23.72 microg/mL (or 6.33microg/cm2) and 118.60 microg/mL (or 31.63 microg/cm2), respectively. The VOC and/or PAH-coated onto PM induced significant increases in mRNA expressions of cytochrome P450 (cyp) 1a1, cyp2e1, cyp2f1, nadph quinone oxydo-reductase-1, and glutathione s-transferase-pi 1, versus controls. Hence, we concluded that the metabolic activation of the very low doses of VOC and/or PAH-coated onto the inorganic condensation nuclei from Dunkerque City's PM is one of the underlying mechanisms of action closely involved in its cytotoxicity in human lung epithelial cells.