Eosinophils Restrict Diesel Exhaust Particles Induced Cell Proliferation of Lung Epithelial A549 Cells, Vial Interleukin-13 Mediated Mechanisms: Implications for Tissue Remodelling And Fibrosis

Background: Diesel exhaust particulates (DEPs) affect lung physiology and cause serious damage to the lungs. A number of studies demonstrated that, eosinophils play a very important role in the development of tissue remodelling and fibrosis of lungs. However, the exact mechanism of pathogenesis of tissue remodelling and fibrosis is not known. Methods: Both in vitro and in vivo models were used in the study. HL-60 and A549 cells were used in the study. Balb/C mice of 8 to 12 weeks old were used for in vivo study. Cell viability by MTT assay, RNA isolation by tri reagent was accomplished. mRNA expression of inflammatory genes were accomplished by real time PCR or qPCR. Immunohistochemistry was done to asses the localization and expressions of proteins. One way ANOVA followed by post hoc test were done for the statistical analysis. Graph-Pad Prism software was used for statistical analysis. Results: We for the first time demonstrate that, Interleukin-13 plays a very important role in the development of tissue remodelling and fibrosis. We report that, diesel exhaust particles significantly induce eosinophils cell proliferation and interleukin-13 release in in vitro culture conditions. Supernatant collected from DEP-induced eosinophils cells significantly restrict cell proliferation of epithelial cells in response to exposure of diesel exhast particles. Furthermore, purified interleukin-13 decreases the proliferation of A549 cells, highliting the involvement of IL-13 in tissue remodeling. Notably, Etoricoxib (selective COX-2 inhibitor) did not inhibit DEP-triggered release of interleukin-13, suggesting another cell signalling pathway. The in vivo exposer of DEP to the lungs of mice, resulted in high level of eosinophils degranulation as depicted by the EPX-1 immunostaining and altered level of mRNA expressions of inflammatory genes. We also found that, a-SMA, fibroblast specific protein (FSP-1) has been changed in response to DEP in the mice lungs along with the mediators of inflammation. Conclusion: Altogether, we elucidated, the mechanistic role of eosinophils and IL-13 in the DEP-triggered proliferation of lungs cells thus providing an inside in the pathophysiology of tissue remodelling and fibrosis of lungs.

The Salutary Effects of Catalpol on Diesel Exhaust Particles-Induced Thrombogenic Changes and Cardiac Oxidative Stress, Inflammation and Apoptosis

Inhaled particulate air pollution exerts pulmonary inflammation and cardiovascular toxicity through secondary systemic effects due to oxidative stress and inflammation. Catalpol, an iridiod glucoside, extracted from the roots of Rehmannia glutinosa Libosch, has been reported to possess anti-inflammatory and antioxidant properties. Yet, the potential ameliorative effects of catalpol on particulate air pollution—induced cardiovascular toxicity, has not been studied so far. Hence, we evaluated the possible mitigating mechanism of catalpol (5 mg/kg) which was administered to mice by intraperitoneal injection one hour before the intratracheal (i.t.) administration of a relevant type of pollutant particle, viz. diesel exhaust particles (DEPs, 30 µg/mouse). Twenty-four hours after the lung deposition of DEPs, several cardiovascular endpoints were evaluated. DEPs caused a significant shortening of the thrombotic occlusion time in pial microvessels in vivo, induced platelet aggregation in vitro, and reduced the prothrombin time and the activated partial thromboplastin time. All these actions were effectively mitigated by catalpol pretreatment. Likewise, catalpol inhibited the increase of the plasma concentration of C-reactive proteins, fibrinogen, plasminogen activator inhibitor-1 and P- and E-selectins, induced by DEPs. Moreover, in heart tissue, catalpol inhibited the increase of markers of oxidative (lipid peroxidation and superoxide dismutase) and nitrosative (nitric oxide) stress, and inflammation (tumor necrosis factor α, interleukin (IL)-6 and IL-1β) triggered by lung exposure to DEPs. Exposure to DEPs also caused heart DNA damage and increased the levels of cytochrome C and cleaved caspase, and these effects were significantly diminished by the catalpol pretreatment. Moreover, catalpol significantly reduced the DEPs-induced increase of the nuclear factor κB (NFκB) in the heart. In conclusion, catalpol significantly ameliorated DEPs–induced procoagulant events and heart oxidative and nitrosative stress, inflammation, DNA damage and apoptosis, at least partly, through the inhibition of NFκB activation.

Measurement report: Ambient volatile organic compounds (VOCs) pollution at urban Beijing: characteristics, sources, and implications for pollution control

The increasing ozone (O3) pollution and high fraction of secondary organic aerosols (SOA) in fine particle mass highlighted the importance of volatile organic compounds (VOCs) in air pollution control. In this work, a campaign of comprehensive field observations was conducted at an urban site in Beijing, from December 2018 to November 2019, to identify the composition, sources, and secondary transformation potential of VOCs. The total mixing ratio of the 95 quantified VOCs (TVOC) observed in this study ranged from 5.5–118.7 ppbv with the mean value of 34.9 ppbv, and the contemporaneous mixing ratios of TVOC was significantly lower than those observed in 2014 and 2016, confirming the effectiveness of VOCs emission control measures in Beijing in recent years. Alkanes, OVOCs and halocarbons were the dominant chemical groups, accounting for 75–81 % of the TVOCs across the sampling months. High and low-O3/PM2.5 months as well as several O3/PM2.5 polluted days were identified during the sampling period. By deweathered calculation, we found that high O3/PM2.5 levels were due to both enhanced precursor emission levels and meteorological conditions favorable to O3 and PM2.5 production. The molar ratios of VOCs to NOX indicated that O3 formation was limited by VOCs during the whole sampling period. Diesel exhaust and industrial emission were identified as the major VOCs sources on both O3-polluted and PM2.5-polluted days based on positive matrix factorization (PMF) analysis, accounting for 46 % and 53 %, respectively. Moreover, higher proportion of oil/gas evaporation was observed on O3-polluted days (18 %) than that on O3-clean days (13 %), and higher proportion of coal/biomass combustion was observed on PM2.5-polluted days (18 %) than that on PM2.5-clean days (13 %). On the base of O3 formation impact, VOCs from fuel evaporation and diesel exhaust particularly toluene, xylenes, trans-2-butene, acrolein, methyl methacrylate, vinyl acetate, 1-butene and 1-hexene were the main contributors, illustrating the necessity of conducting emission controls on these pollution sources and species for alleviating O3 pollution. Instead, VOCs from diesel exhaust and coal/biomass combustion were found to be the dominant contributors for secondary organic aerosol formation potential (SOAFP), particularly the VOC species of toluene, 1-hexene, xylenes, ethylbenzene and styrene, and top priority should be given to these for the alleviation of haze pollution. The positive matrix factorization (PSCF) analysis showed that O3 and PM2.5 pollution was mainly affected by local emissions. This study provides insights for government to formulate effective VOCs control measures for air pollution in Beijing.

Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury

Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.001), 100 (p=0.001), and 200 hours (p<0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.

Acute Diesel Exhaust Exposure Causes a Delayed Reduction in Cognitive Control

Urban residents are frequently exposed to high levels of traffic-derived air pollution for short time periods, often (but not exclusively) during commuting. Although chronic air pollution exposure and health effects, including neurological effects on children and older adults, are known to be correlated, causal effects of acute pollution exposure on brain function in healthy young adults remain sparsely investigated. Neuroinflammatory accounts suggest effects could be delayed by several hours and could affect attention, especially in social contexts. Using a controlled atmosphere chamber, we exposed 81 healthy young adults to either diluted diesel exhaust (equivalent to polluted roadside environments) or clean air for one hour. Half of each group immediately completed a selective attention task to assess cognitive control; remaining participants completed the task after a 4-hour delay. Cognitive control was significantly poorer after diesel versus clean air exposure for those in the delay but not immediate test condition, suggesting an inflammatory basis for this acute negative effect of air pollution on cognition. These findings provide the first experimental evidence that acute diesel exposure, comparable to polluted city streets, causes a negative effect on cognitive control several hours later. These findings may explain commuter mental fatigue and support clean-air initiatives.