Transcriptomic analysis identifies dysregulated genes and functional networks in human small airway epithelial cells exposed to ambient PM2.5.

Cellular models exhibiting human physiological features of pseudostratified columnar epithelia, provide a more realistic approach for elucidating detailed mechanisms underlying PM2.5-induced pulmonary toxicity. In this study, we characterized the barrier and mucociliary functions of differentiated human small airway epithelial cells (SAECs), cultured at the air-liquid interface (ALI). Due to the presence of mucociliary protection, particle internalization was reduced, with a concomitant decrease in cytotoxicity in differentiated S-ALI cells, as compared to conventional submerged SAEC cultures. After 24-hour exposure to PM2.5 surrogates, 117 up-regulated genes and 156 down-regulated genes were detected in S-ALI cells, through transcriptomic analysis using the Affymetrix Clariom™ S Human Array. Transcription-level changes in >60 signaling pathways, were revealed by functional annotation of the 273 differentially expressed genes, using the PANTHER Gene List Analysis. These pathways are involved in multiple cellular processes, that include inflammation and apoptosis. Exposure to urban PM2.5 led to complex responses in airway epithelia, including a net induction of downstream pro-inflammatory and pro-apoptotic responses. Collectively, this study highlights the importance of using the more advanced ALI model rather than the undifferentiated submerged model, to avoid over-assessment of inhaled particle toxicity in human. The results of our study also suggest that reduction of ambient PM2.5 concentrations would have a protective effect on respiratory health in humans.

Urban PM2.5 reduces angiogenic ability of endothelial cells in an alveolar-capillary co-culture lung model.

Adverse health effects arising from exposure to fine particulates have become a major concern. Angiogenesis is a vital physiological process for the growth and development of cells and structures in the human body, whereby excessive or insufficient vessel growth could contribute to pathogenesis of diseases. We therefore evaluated indirect effects of carbon black (CB) and inhalable airborne particles on the angiogenic ability of unexposed Human Umbilical Vein Endothelial Cells (HUVECs) by co-culturing HUVECs with pre-exposed Small Airway Epithelial Cells (SAECs). As endothelial cells are major components of blood vessels and potential targets of fine particles, we investigated if lung epithelial cells exposed to ambient PM2.5 surrogates could induce bystander effects on neighboring unexposed endothelial cells in an alveolar-capillary co-culture lung model. Epithelial exposure to CB at a non-toxic dose of 25 µg/mL reduced endothelial tube formation and cell adhesion in co-cultured HUVECs, and decreased expression of angiogenic genes in SAECs. Similarly, exposure of differentiated SAECs to PM2.5 surrogates reduced cell reproductive ability, adhesion and tube formation of neighboring HUVECs. This indicates epithelial exposure to CB and urban PM2.5 surrogates both compromised the angiogenic ability of endothelial cells through bystander effects, thereby potentially perturbing the ventilation-perfusion ratio and affecting lung function.

Toxicity Study of Zinc Oxide Nanoparticles in Cell Culture and in Drosophila melanogaster.

Zinc oxide nanoparticles (ZnO NPs) have a wide range of applications, but the number of reports on ZnO NP-associated toxicity has grown rapidly in recent years. However, studies that elucidate the underlying mechanisms for ZnO NP-induced toxicity are scanty. We determined the toxicity profiles of ZnO NPs using both in vitro and in vivo experimental models. A significant decrease in cell viability was observed in ZnO NP-exposed MRC5 lung fibroblasts, showing that ZnO NPs exert cytotoxic effects. Similarly, interestingly, gut exposed to ZnO NPs exhibited a dramatic increase in reactive oxygen species levels (ROS) in the fruit fly Drosophila. More in-depth studies are required to establish a risk assessment for the increased usage of ZnO NPs by consumers.

Impacts of peat-forest smoke on urban PM2.5 in the Maritime Continent during 2012-2015: Carbonaceous profiles and indicators.

This study characterizes impacts of peat-forest (PF) smoke on an urban environment through carbonaceous profiles of >260 daily PM2.5 samples collected during 2012, 2013 and 2015. Organic carbon (OC) and elemental carbon (EC) comprising eight carbonaceous fractions are examined for four sample groups - non-smoke-dominant (NSD), smoke-dominant (SD), episodic PM2.5 samples at the urban receptor, and near-source samples collected close to PF burning sites. PF smoke introduced much larger amounts of OC than EC, with OC accounting for up to 94% of total carbon (TC), or increasing by up to 20 times in receptor PM2.5. SD PM2.5 at the receptor site and near-source samples have OC3 and EC1 as the dominant fractions. Both sample classes also exhibit char-EC >1.4 times of soot-EC, characterizing smoldering-dominant PF smoke, unlike episodic PM2.5 at the receptor site featuring large amounts of pyrolyzed organic carbon (POC) and soot-EC. Relative to the mean NSD PM2.5 at the receptor, increasing strength of transboundary PF smoke enriches OC3 and OC4 fractions, on average, by factors of >3 for SD samples, and >14 for episodic samples. A peat-forest smoke (PFS) indicator, representing the concentration ratio of (OC2+OC3+POC) to soot-EC, shows a temporal trend satisfactorily correlating with an organic marker (levoglucosan) of biomass burning. The PFS indicator systematically differentiates influences of PF smoke from source to urban receptor sites, with a progressive mean of 3.6, 13.4 and 20.1 for NSD, SD and episodic samples respectively at the receptor site, and 54.7 for the near-source PM2.5. A PFS indicator of ≥5.0 is proposed to determine dominant influence of transboundary PF smoke on receptor urban PM2.5 in the equatorial Asia with ∼90% confidence. Assessing >2900 hourly OCEC data in 2017-2018 supports the applicability of the PFS indicator to evaluate hourly impacts of PF smoke on receptor urban PM2.5 in the Maritime Continent.