Indoor and ambient black carbon and fine particulate matter associations with blood biomarkers in COPD patients.

BACKGROUND: Systemic inflammation contributes to cardiovascular risk and chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between systemic inflammation and exposure to ambient fine particulate matter (PM ≤ 2.5 µm diameter; PM2.5), and black carbon (BC), a PM2.5 component attributable to traffic and other sources of combustion, infiltrating indoors are not well described. METHODS: Between 2012 and 2017, COPD patients completed in-home air sampling over one-week intervals, up to four times (seasonally), followed by measurement of plasma biomarkers of systemic inflammation, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activation, soluble vascular adhesion molecule-1 (sVCAM-1). Ambient PM2.5, BC and sulfur were measured at a central site. The ratio of indoor/ambient sulfur in PM2.5, a surrogate for fine particle infiltration, was used to estimate indoor BC and PM2.5 of ambient origin. Linear mixed effects regression with a random intercept for each participant was used to assess associations between indoor and indoor of ambient origin PM2.5 and BC with each biomarker. RESULTS: 144 participants resulting in 482 observations were included in the analysis. There were significant positive associations between indoor BC and indoor BC of ambient origin with CRP [%-increase per interquartile range (IQR);95 % CI (13.2 %;5.2-21.8 and 11.4 %;1.7-22.1, respectively)]. Associations with indoor PM2.5 and indoor PM2.5 of ambient origin were weaker. There were no associations with IL-6 or sVCAM-1. CONCLUSIONS: In homes of patients with COPD without major sources of combustion, indoor BC is mainly attributable to the infiltration of ambient sources of combustion indoors. Indoor BC of ambient origin is associated with increases in systemic inflammation in patients with COPD, even when staying indoors.

Long-term mortality burden trends attributed to black carbon and PM2·5 from wildfire emissions across the continental USA from 2000 to 2020: a deep learning modelling study.

BACKGROUND: Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM2·5 concentrations and their attributable mortality burden across the USA. METHODS: In this study, we derived daily concentrations of PM2·5 and its highly toxic black carbon component at a 1-km resolution in the USA from 2000 to 2020 via deep learning that integrated big data from satellites, models, and surface observations. We estimated the annual PM2·5-attributable and black carbon-attributable mortality burden at each 1-km2 grid using concentration-response functions collected from a national cohort study and a meta-analysis study, respectively. We investigated the spatiotemporal linear-regressed trends in PM2·5 and black carbon pollution and their associated premature deaths from 2000 to 2020, and the impact of wildfires on air quality and public health. FINDINGS: Our results showed that PM2·5 and black carbon estimates are reliable, with sample-based cross-validated coefficients of determination of 0·82 and 0·80, respectively, for daily estimates (0·97 and 0·95 for monthly estimates). Both PM2·5 and black carbon in the USA showed significantly decreasing trends overall during 2000 to 2020 (22% decrease for PM2·5 and 11% decrease for black carbon), leading to a reduction of around 4200 premature deaths per year (95% CI 2960-5050). However, since 2010, the decreasing trends of fine particles and premature deaths have reversed to increase in the western USA (55% increase in PM2·5, 86% increase in black carbon, and increase of 670 premature deaths [460-810]), while remaining mostly unchanged in the eastern USA. The western USA showed large interannual fluctuations that were attributable to the increasing incidence of wildfires. Furthermore, the black carbon-to-PM2·5 mass ratio increased annually by 2·4% across the USA, mainly due to increasing wildfire emissions in the western USA and more rapid reductions of other components in the eastern USA, suggesting a potential increase in the relative toxicity of PM2·5. 100% of populated areas in the USA have experienced at least one day of PM2·5 pollution exceeding the daily air quality guideline level of 15 µg/m3 during 2000-2020, with 99% experiencing at least 7 days and 85% experiencing at least 30 days. The recent widespread wildfires have greatly increased the daily exposure risks in the western USA, and have also impacted the midwestern USA due to the long-range transport of smoke. INTERPRETATION: Wildfires have become increasingly intensive and frequent in the western USA, resulting in a significant increase in smoke-related emissions in populated areas. This increase is likely to have contributed to a decline in air quality and an increase in attributable mortality. Reducing fire risk via effective policies besides mitigation of climate warming, such as wildfire prevention and management, forest restoration, and new revenue generation, could substantially improve air quality and public health in the coming decades. FUNDING: National Aeronautics and Space Administration (NASA) Applied Science programme, NASA MODIS maintenance programme, NASA MAIA satellite mission programme, NASA GMAO core fund, National Oceanic and Atmospheric Administration (NOAA) GEO-XO project, NOAA Atmospheric Chemistry, Carbon Cycle, and Climate (AC4) programme, and NOAA Educational Partnership Program with Minority Serving Institutions.

Ambient black carbon reaches the kidneys.

BACKGROUND: Ultrafine particles, including black carbon (BC), can reach the systemic circulation and therefore may distribute to distant organs upon inhalation. The kidneys may be particularly vulnerable to the adverse effects of BC exposure due to their filtration function. OBJECTIVES: We hypothesized that BC particles reach the kidneys via the systemic circulation, where the particles may reside in structural components of kidney tissue and impair kidney function. METHODS: In kidney biopsies from 25 transplant patients, we visualized BC particles using white light generation under femtosecond-pulsed illumination. The presence of urinary kidney injury molecule-1 (KIM-1) and cystatin c (CysC) were evaluated with ELISA. We assessed the association between internal and external exposure matrices and urinary biomarkers using Pearson correlation and linear regression models. RESULTS: BC particles could be identified in all biopsy samples with a geometric mean (5th, 95th percentile) of 1.80 × 103 (3.65 × 102, 7.50 × 103) particles/mm3 kidney tissue, predominantly observed in the interstitium (100 %) and tubules (80 %), followed by the blood vessels and capillaries (40 %), and the glomerulus (24 %). Independent from covariates and potential confounders, we found that each 10 % higher tissue BC load resulted in 8.24 % (p = 0.03) higher urinary KIM-1. In addition, residential proximity to a major road was inversely associated with urinary CysC (+10 % distance: -4.68 %; p = 0.01) and KIM-1 (+10 % distance: -3.99 %; p < 0.01). Other urinary biomarkers, e.g., the estimated glomerular filtration rate or creatinine clearance showed no significant associations. DISCUSSION AND CONCLUSION: Our findings that BC particles accumulate near different structural components of the kidney represent a potential mechanism explaining the detrimental effects of particle air pollution exposure on kidney function. Furthermore, urinary KIM-1 and CysC show potential as air pollution-induced kidney injury biomarkers for taking a first step in addressing the adverse effects BC might exert on kidney function.

Curcuma longa supplementation reduces MDA, TNF-α, and IL-6 levels in a rat model exposed to soot particulates.

Background: Particulate matter (PM) is one of the important components in air pollution that can cause endothelial vascular dysfunction through exacerbation of atherosclerosis and inflammation of the respiratory system. Increased levels of malondialdehyde (MDA) in blood plasma can be an indicator of oxidative stress. Then, macrophages can secrete proinflammatory cytokines that will stimulate immune cells and vascular endothelial cells to release inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrotic factor-α (TNF-α). Curcuma longa works by scavenging the active free radicals involved in the peroxidation process. Aims: This study aims to prove that the administration of C. longa can reduce MDA, TNF-α, and IL-6 levels in Rattus norvegicus exposed to soot particulates. Methods: The subjects of this study were 30 male rats which were divided into 5 treatment groups with the following: (C0): negative control; (C+): positive control; (T1): Treatment group 2, rats exposed to particulate soot at a concentration of 1,064 mg/m3 for 8 hours and given C. longa at a dose of 1 mg/kg bw; (T2): Treatment group 3 was rats exposed to soot particulates at a concentration of 1,064 mg/m3 for 8 hours and given C. longa at a dose of 2 mg/kg bw; (T3): Treatment group 4 was rats exposed to soot particulates at a concentration of 1,064 mg/m3 for 8 hours and given C. longa at a dose of 3 mg/kg bw.Giving the C. longa extract orally with a probe every day for 30 days after treatment of exposure to soot. Examination of MDA, TNF-, and IL-6 levels with the ELISA method. Results: The administration of C. longa can reduce MDA while the lowest MDA levels were obtained in the T3 treatment with an average of 1.542 ± 0.231. The results of the description of the lowest levels of TNF-α were obtained in the C-treatment with an average of 55.981 ± 4.689. Then, the lowest levels of IL-6 were obtained in the C-treatment with an average of 2.292 ± 0.461. Conclusion: The results stated that the administration of C. longa could reduce MDA levels, TNF-α, and IL-6 levels. Curcuma longa as an anti-inflammatory and anti-oxidant play an effective role in inhibiting inflammation by decreasing IL-6 cytokine and TNF-α. Curcuma longa can inhibit lipid peroxidation initiated by free radicals and then reduce MDA levels.

Black carbon content in airway macrophages is associated with increased severe exacerbations and worse COPD morbidity in SPIROMICS.

BACKGROUND: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown. METHODS: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (<$35,000, $35,000~$74,999, ≥$75,000, decline to answer), BMI, and use of long-acting beta-agonist/long-acting muscarinic antagonists, with sensitivity analysis performed with inclusion of urinary cotinine and lung function as covariates. RESULTS: Of 324 participants, 143 were current smokers and 201 had spirometric-confirmed COPD. Modeled indoor fine (< 2.5 µm in aerodynamic diameter) particulate matter (PM2.5) and urinary cotinine were associated with higher AM BC. Other assessed indoor and ambient pollutant exposures were not associated with higher AM BC. Higher AM BC was associated with worse lung function and odds of severe exacerbation, as well as worse functional status, respiratory symptoms and quality of life. CONCLUSION: Indoor PM2.5 and cigarette smoke exposure may lead to increased AM BC deposition. Black carbon content in AMs is associated with worse COPD morbidity in current and former smokers, which remained after sensitivity analysis adjusting for cigarette smoke burden. Airway macrophage BC, which may alter macrophage function, could serve as a predictor of experiencing worse respiratory symptoms and impaired lung function.

Ambient air pollution exposure and depressive symptoms: Findings from the French CONSTANCES cohort.

BACKGROUND AND AIM: Few studies have reported the association between air pollution exposure with different dimensions of depression. We aimed to explore this association across different dimensions of depressive symptoms in a large population. METHODS: Data from the enrollment phase of the French CONSTANCES cohort (2012-2020) were analyzed cross-sectionally. Annual concentrations of particulate matter with a diameter < 2.5 µm (PM2.5), black carbon (BC), and nitrogen dioxide (NO2) from the land-use regression models were assigned to the residential addresses of participants. Total depressive symptoms and its four dimensions (depressed affect, disturbed interpersonal relations, low positive affect, somatic complaints) were measured using Centre of Epidemiologic Studies Depression questionnaire (CES-D). We reported results of negative binomial regression models (reported as Incidence Rate Ratio (IRR) and 95 % confidence interval (CI) for an interquartile range (IQR) increase in exposure), for each pollutant separately. Stratified analyses were performed by sex, income, family status, education, and neighborhood deprivation. RESULTS: The study included 123,754 participants (mean age, 46.50 ± 13.61 years; 52.4 % women). The mean concentration of PM2.5, BC and NO2 were 17.14 µg/m3 (IQR = 4.89), 1.82 10-5/m (IQR = 0.88) and 26.58 µg/m3 (IQR = 17.41) respectively. Exposures to PM2.5, BC and NO2 were significantly associated with a higher CES-D total (IRR = 1.022; 95 % CI = 1.002: 1.042, IRR = 1.027; 95 % CI = 1.013: 1.040, and IRR = 1.029; 95 % CI = 1.015: 1.042 respectively), and with depressed affect, and somatic complaints. For all pollutants, a higher estimate was observed for depressed affect. We found stronger adverse associations for men, lower-income participants, low and middle education groups, those living in highly deprived areas, and single participants. CONCLUSION: Our finding could assist the exploration of the etiological pathway of air pollution on depression and also considering primary prevention strategies in the areas with air pollution.

Maternal exposure to ambient black carbon particles and their presence in maternal and fetal circulation and organs: an analysis of two independent population-based observational studies.

BACKGROUND: Maternal exposure to particulate air pollution during pregnancy has been linked to multiple adverse birth outcomes causing burden of disease later in the child's life. To date, there is a paucity of data on whether or not ambient particles can both reach and cross the human placenta to exert direct effects on fetal organ systems during gestation. METHODS: In this analysis, we used maternal-perinatal and fetal samples collected within the framework of two independent studies: the ENVIRONAGE (Environmental Influences on Ageing in Early Life) birth cohort of mothers giving birth at the East-Limburg Hospital in Genk, Belgium, and the SAFeR (Scottish Advanced Fetal Research) cohort of terminated, normally progressing pregnancies among women aged 16 years and older in Aberdeen and the Grampian region, UK. From the ENVIRONAGE study, we included 60 randomly selected mother-neonate pairs, excluding all mothers who reported that they ever smoked. From the SAFeR study, we included 36 fetuses of gestational age 7-20 weeks with cotinine concentrations indicative of non-smoking status. We used white light generation under femtosecond pulsed illumination to detect black carbon particles in samples collected at the maternal-fetal interface. We did appropriate validation experiments of all samples to confirm the carbonaceous nature of the identified particles. FINDINGS: We found evidence of the presence of black carbon particles in cord blood, confirming the ability of these particles to cross the placenta and enter the fetal circulation system. We also found a strong correlation (r ≥0·50; p<0·0001) between the maternal-perinatal particle load (in maternal blood [n=60], term placenta [n=60], and cord blood [n=60]) and residential ambient black carbon exposure during pregnancy. Additionally, we found the presence of black carbon particles in first and second trimester tissues (fetal liver [n=36], lung [n=36], and brain [n=14]) of electively terminated and normally progressing pregnancies from an independent study. INTERPRETATION: We found that maternally inhaled carbonaceous air pollution particles can cross the placenta and then translocate into human fetal organs during gestation. These findings are especially concerning because this window of exposure is key to organ development. Further studies are needed to elucidate the mechanisms of particle translocation. FUNDING: European Research Council, Flemish Scientific Research Foundation, Kom op Tegen Kanker, UK Medical Research Council, and EU Horizon 2020.

Long-term exposure to ambient black carbon is associated with sleep disturbance in college students.

BACKGROUND: Evidence suggests an association of air pollution with sleep quality. However, there is limited knowledge regarding the effect of black carbon, a key component of ambient particulate matter, on sleep. OBJECTIVES: To investigate the association of long-term exposure to black carbon and sleep quality in a group of college students. METHODS: A retrospective cohort study was conducted in five universities in different regions of China. The concentrations of black carbon and other environment factors were defined as the averages during the 6 years prior to the recruitment. Averagely daily dose of black carbon exposure was estimated according to the respiratory rate. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) with a cutoff >5 indicating sleep disturbance. Linear regression and logistic regression models were used to estimate the association. The sensitivity analyses were conducted to estimate the effects of 1-month, 6-month and 1-year mean levels of exposure to black carbon on sleep quality. RESULTS: A total of 20,053 incoming college students were included. 29.3% reported impaired sleep quality, with a mean PSQI score of 4.3 ± 2.2. The logistic regression showed that the risk of impaired sleep quality was positively associated with black carbon exposure, especially in the highest quantile (OR: 1.26, 95% CI: 1.11-1.43) compared with the lowest quartile after adjusting for potential confounders. Subgroup analysis showed that the effect of black carbon on sleep quality was stronger in participants with higher BMI, lower household income, and lower parental educational level. The results of sensitivity analyses were similar with main analyses. CONCLUSION: Long-term exposure to black carbon is associated with sleep disturbance in college students. Improvement of air quality may help improve sleep quality.

Effect of NLRP3 repression on NLRP3 inflammasome activation in human corneal epithelial cells with black carbon exposure.

PURPOSE: To investigate the inhibitory effects of NLRP3 siRNA on NLRP3 inflammasome activation in human corneal epithelial cells (HCECs) with fresh black carbon (FBC) particles and ozone-oxidized BC (OBC) particles treatment. METHODS: HCECs were transfected with NLRP3 siRNA or control siRNA for 48 h, followed by 200 µg/ml FBC or OBC suspension for an additional 72 h. Untreated controls were cells with no siRNA transfection or BC treatment. RT-qPCR and Western blot were used to measure mRNA and protein levels of components of the NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) and downstream cytokine (IL-1ß), respectively. RESULTS: Compared with untreated control cells, mRNA levels of NLRP3, ASC, Caspase-1, and IL-1ß were significantly higher (p < 0.05) in control siRNA transfected cells with BC treatments. Compared with the control siRNA transfected cells, NLRP3 siRNA transfection reduced the expression of NLRP3 and ASC, whereas it had a limited effect on the expression of Caspase-1 and IL-1ß with FBC or OBC exposures. Under FBC treatment, the reductions of NLRP3 and Caspase-1 mRNA levels were 53.5% (p < 0.001) and 34.2% (p < 0. 01), respectively, and NLRP3 and ASC protein levels were lowered by 58.2% (p < 0.001) and 45.4% (p < 0.001), respectively. Under OBC treatment, the reductions of NLRP3 and Caspase-1 mRNA levels were 39.8% (p < 0.001) and 25.6% (p < 0.05), respectively, and NLRP3 and ASC protein levels were lowered by 44.8% (p < 0.001) and 41.7% (p < 0.001), respectively. Moreover, mRNA levels of ASC and IL-1ß, the protein levels of Caspase-1 and IL-1ß showed a tendency to decrease in NLRP3 siRNA transfected cells, it was statistically insignificant (p > 0.05). CONCLUSIONS: NLRP3 siRNA transfection could partially reverse the increased mRNA levels of NLRP3 and Caspase-1, the protein levels of NLRP3 and ASC in HCECs with BC treatment, whereas the reductions of protein levels of Caspase-1 and IL-1ß were not significant, indicating that NLRP3 siRNA has a limited inhibitory effect on the activation of NLRP3 inflammasome triggered by BC.

RIPK1 is a key factor in black carbon-induced cell death.

Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.

Modification of associations between indoor particulate matter and systemic inflammation in individuals with COPD.

RATIONALE: Little is known about personal characteristics and systemic responses to particulate pollution in patients with COPD. OBJECTIVES: Assess whether diabetes, obesity, statins and non-steroidal anti-inflammatory medications (NSAIDs) modify associations between indoor black carbon (BC) and fine particulate matter ≤2.5 µm in diameter (PM2.5) on systemic inflammation and endothelial activation. METHODS: 144 individuals with COPD without current smoking and without major in-home combustion sources were recruited at Veterans Affairs Boston Healthcare System. PM2.5 and BC were measured in each participant's home seasonally for a week (up to 4 times; 482 observations) and plasma biomarkers of systemic inflammation [C-reactive protein (CRP); interleukin-6 (IL-6)] and endothelial activation [soluble vascular adhesion molecule-1 (sVCAM-1)] measured. Linear mixed effects regression with a random intercept was used, and effect modification assessed with multiplicative interaction terms and stratum specific estimates. RESULTS: Median (25%ile, 75%ile) indoor BC and PM2.5 were 0.6 (0.5,0.7) µg/m3 and 6.8 (4.8,10.4) µg/m3, respectively. Although p-values for effect modification were not statistically significant, there were positive associations (%-increase/interquartile range; 95% CI) between CRP and BC greater among non-statin (18.8%; 3.6-36.3) than statin users (11.1%; 2.1-20.9). There were also positive associations greater among non-statin users between PM2.5 and CRP. For IL-6, associations with BC and PM2.5 were also greater among non-statin users. Associations between CRP and BC were greater (20.3%; 4.5-38.5) in persons with diabetes than without diabetes (10.3%; 0.92-20.6) with similar effects of PM2.5. There were no consistent associations that differed based on obesity. Effect modification was not observed for NSAID use, or with any factor considered with sVCAM-1. CONCLUSIONS: Associations between indoor BC and PM2.5 and CRP were greater in patients with diabetes and those not taking statins, and with IL-6 if not taking statins. These results suggest that these characteristics may modify the systemic response to indoor BC and PM2.5 in persons with COPD.

The effect of air pollution on the transcriptomics of the immune response to respiratory infection.

Combustion related particulate matter air pollution (PM) is associated with an increased risk of respiratory infections in adults. The exact mechanism underlying this association has not been determined. We hypothesized that increased concentrations of combustion related PM would result in dysregulation of the innate immune system. This epidemiological study includes 111 adult patients hospitalized with respiratory infections who underwent transcriptional analysis of their peripheral blood. We examined the association between gene expression at the time of hospitalization and ambient measurements of particulate air pollutants in the 28 days prior to hospitalization. For each pollutant and time lag, gene-specific linear models adjusting for infection type were fit using LIMMA (Linear Models For Microarray Data), and pathway/gene set analyses were performed using the CAMERA (Correlation Adjusted Mean Rank) program. Comparing patients with viral and/or bacterial infection, the expression patterns associated with air pollution exposure differed. Adjusting for the type of infection, increased concentrations of Delta-C (a marker of biomass smoke) and other PM were associated with upregulation of iron homeostasis and protein folding. Increased concentrations of black carbon (BC) were associated with upregulation of viral related gene pathways and downregulation of pathways related to antigen presentation. The pollutant/pathway associations differed by lag time and by type of infection. This study suggests that the effect of air pollution on the pathogenesis of respiratory infection may be pollutant, timing, and infection specific.

Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers.

Nanoscale carbon black as virtually pure elemental carbon can deposit deep in the lungs and cause pulmonary injury. Airway remodeling assessed using computed tomography (CT) correlates well with spirometry in patients with obstructive lung diseases. Structural airway changes caused by carbon black exposure remain unknown. Wall and lumen areas of sixth and ninth generations of airways in 4 lobes were quantified using end-inhalation CT scans in 58 current carbon black packers (CBPs) and 95 non-CBPs. Carbon content in airway macrophage (CCAM) in sputum was quantified to assess the dose-response. Environmental monitoring and CCAM showed a much higher level of elemental carbon exposure in CBPs, which was associated with higher wall area and lower lumen area with no change in total airway area for either airway generation. This suggested small airway wall thickening is a major feature of airway remodeling in CBPs. When compared with wall or lumen areas, wall area percent (WA%) was not affected by subject characteristics or lobar location and had greater measurement reproducibility. The effect of carbon black exposure status on WA% did not differ by lobes. CCAM was associated with WA% in a dose-dependent manner. CBPs had lower FEV1 (forced expiratory volume in 1 s) than non-CBPs and mediation analysis identified that a large portion (41-72%) of the FEV1 reduction associated with carbon black exposure could be explained by WA%. Small airway wall thickening as a major imaging change detected by CT may underlie the pathology of lung function impairment caused by carbon black exposure.

Carbon black nanoparticles induce HDAC6-mediated inflammatory responses in 16HBE cells.

Long-term inhalation of carbon black nanoparticles (CBNPs) leads to pulmonary inflammatory diseases. Histone deacetylase 6 (HDAC6) has been identified as an important regulator in the development of inflammatory disorders. However, the direct involvement of HDAC6 in CBNPs-induced pulmonary inflammatory responses remains unclear. To explore whether HDAC6 participates in CBNPs-induced pulmonary inflammation, human bronchial epithelial cell line (16HBE cells) was transfected with HDAC6 small interference RNA (siRNA) and then exposed to CBNPs at concentrations of 0, 25, and 50 µg/ml for 24 h. Intracellular HDAC6 and intraflagellar transport protein 88 (IFT88) mRNA and protein were determined by real-time polymerase chain reaction and Western blot, respectively. The secretions of inflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, IL-6, and IL-1ß were measured by enzyme-linked immunosorbent assay. CBNPs induced a significant increase in the expressions of IL-8 and IL-6, accompanied by a high level of intracellular HDAC6 mRNA when compared with a blank control group (p < 0.05). However, there were no significant changes in the levels of TNF-α secretion, intracellular HDAC6 and IFT88 protein induced by CBNPs (p > 0.05). The HDAC6 mRNA expression was significantly suppressed in HDAC6 siRNA-transfected cells (p < 0.05). The secretions of IL-8, TNF-α, and IL-6 were significantly less in HDAC6 siRNA-transfected cells than that in normal 16HBE cells with exposure to 25 or 50 µg/ml of CBNPs, but intracellular IFT88 mRNA expression was markedly increased in HDAC6 siRNA-transfected cells when compared with normal 16HBE cells exposed to 50 µg/ml of CBNPs (all p < 0.05). Downregulation of the HDAC6 gene inhibits CBNPs-induced inflammatory responses in bronchial epithelial cells, partially through regulating IFT88 expression. It is suggested that CBNPs may trigger inflammatory responses in bronchial epithelial cells by an HDAC6/IFT88-dependent pathway.

Intracranial tumors of the central nervous system and air pollution - a nationwide case-control study from Denmark.

BACKGROUND: Inconclusive evidence has suggested a possible link between air pollution and central nervous system (CNS) tumors. We investigated a range of air pollutants in relation to types of CNS tumors. METHODS: We identified all (n = 21,057) intracranial tumors in brain, meninges and cranial nerves diagnosed in Denmark between 1989 and 2014 and matched controls on age, sex and year of birth. We established personal 10-year mean residential outdoor exposure to particulate matter < 2.5 µm (PM2.5), nitrous oxides (NOX), primary emitted black carbon (BC) and ozone. We used conditional logistic regression to calculate odds ratios (OR) linearly (per interquartile range (IQR)) and categorically. We accounted for personal income, employment, marital status, use of medication as well as socio-demographic conditions at area level. RESULTS: Malignant tumors of the intracranial CNS was associated with BC (OR: 1.034, 95%CI: 1.005-1.065 per IQR. For NOx the OR per IQR was 1.026 (95%CI: 0.998-1.056). For malignant non-glioma tumors of the brain we found associations with PM2.5 (OR: 1.267, 95%CI: 1.053-1.524 per IQR), BC (OR: 1.049, 95%CI: 0.996-1.106) and NOx (OR: 1.051, 95% CI: 0.996-1.110). CONCLUSION: Our results suggest that air pollution is associated with malignant intracranial CNS tumors and malignant non-glioma of the brain. However, additional studies are needed.

Carbon nanoparticles induce endoplasmic reticulum stress around blood vessels with accumulation of misfolded proteins in the developing brain of offspring.

Nano-particulate air pollution threatens developing brains and is epidemiologically related to neurodegenerative diseases involving deposition of misfolded proteins. However, the mechanism underlying developmental neurotoxicity by nanoparticles remains unknown. Here, we report that maternal exposure to low doses of carbon black nanoparticle (CB-NP) induces endoplasmic reticulum (ER) stress associated with accumulation of misfolded proteins. Notably, offspring specifically showed high induction of ER stress in perivascular macrophages and reactive astrocytes only around brain blood vessels, along with accumulation of ß-sheet-rich proteins regarded as misfolded proteins. Our results suggest that maternal CB-NP exposure induced ER stress in PVMs and reactive astrocytes around blood vessels in the brain of offspring in mice. The induction of ER stress accompanied by the perivascular accumulation of misfolded proteins is likely to be associated with perivascular abnormalities and neurodegeneration, and development of neurodegenerative diseases related to particulate air pollution.

Carbon black nanoparticles induce cell necrosis through lysosomal membrane permeabilization and cause subsequent inflammatory response.

Rationale: The adverse health effects of nano-particulate pollutants have attracted much attention in recent years. Carbon nanomaterials are recognized as risk factors for prolonged inflammatory responses and diffuse alveolar injury. Previous research indicated a central role of alveolar macrophages in the pathogenesis of particle-related lung disease, but the underlying mechanism remains largely unknown. Methods: C57BL/6 mice were intratracheally instilled with carbon black nanoparticles (CBNPs). Cell necrosis and the infiltrated neutrophils in the lungs were detected by flow cytometry. Release of mitochondria was observed with Mito Tracker and mitochondrial DNA (mtDNA) was quantified by qPCR via Taqman probes. TLR9-p38 MAPK signaling pathway was detected by Western blotting. The production of lipid chemoattractant leukotriene B4 (LTB4) in the supernatant and bronchoalveolar lavage fluid (BALF) was quantitated using an enzyme immunoassay (EIA). Results: In the present study, we found that a single instillation of CBNPs induced neutrophil influx in C57BL/6 mice as early as 4 h post-exposure following the rapid appearance of cell damage indicators in BALF at 30 min. Macrophages exposed to CBNPs showed necrotic features and were characterized by lysosome rupture, cathepsin B release, reactive oxygen species generation, and reduced intracellular ATP level. Necrosis was partly inhibited by a specific lysosomal cathepsin B inhibitor CA074 Me. Further analyses suggested that the resulting leakage of mtDNA from the necrotic cells activated neutrophils and triggered severe inflammation in vivo. Pulmonary neutrophilic inflammation induced by mtDNA was reduced in TLR9-/- mice. Additionally, mtDNA induced LTB4 production from macrophages, which may contribute to neutrophil recruitment. Conclusion: We demonstrated here that CBNPs induce acute cell necrosis through lysosomal rupture and that mtDNA released from necrotic cells functions as a key event mediating pulmonary neutrophilic inflammation. This study described a novel aspect of the pathogenesis of particle-induced inflammatory response and provided a possible therapeutic target for the regulation of inflammation.

The Protective Effect of an Eye Wash Solution on the Ocular Surface Damage Induced by Airborne Carbon Black Exposure.

PURPOSE: To investigate the effects of an eye wash solution on the ocular surface damage induced by airborne carbon black (CB) exposure. METHODS: Sprague-Dawley rats were exposed to ambient CB for 5 days. During the 5 days, a commercial eye wash solution (Eyebon-W) was used for irrigation twice daily on CB-exposed rat eyes; normal saline was used as the vehicle control. Lactic dehydrogenase (LDH) activity and matrix metallopeptidase (MMP)-9, histamine, and lactoferrin levels were measured in tears. The expression of inflammatory cytokines in the anterior segment of the eyeball was measured by Western blot analysis. RESULTS: The ocular surface staining scores, tear LDH activity, tear MMP-9, histamine, and lactoferrin concentrations, and the expression of interleukin-4 and interferon-γ in the eye were significantly increased in the CB group versus the normal control group. When compared with CB group, the Eyebon-W eye wash treatment significantly reversed these elevations induced by CB, including ocular staining scores, tear LDH activity, histamine and MMP-9 concentrations in the tear fluid, and the expression of interleukin-4 in the eye. On the other hand, saline irrigation only reduced the concentrations of histamine and MMP-9 in tear fluid and the expression of interferon-γ in the eye. CONCLUSIONS: Both Eyebon-W eye wash treatment and saline irrigation reversed CB-induced ocular surface injury, but the efficacy of Eyebon-W was more significant than that of the saline solution when compared with CB group. The use of an eye wash solution seems to play a protective role for the ocular surface when exposed to airborne particulate matter.