Yuquan Xie

The biological effects of individual-level PM2.5 exposure on systemic immunity and inflammatory response in traffic policemen

Background Ambient fine-particle particulate matter (PM2.5) exposure is associated with the decline in pulmonary function, prevalence of coronary heart disease and incidence of myocardial infarction. The study is to observe the effects of ambient PM2.5 on the cardiovascular system and to explore the potential inflammatory and immune mechanisms. Methods The subjects included 110 traffic policemen in Shanghai, China, who were aged 25–55 years. Two-times continuous 24 h individual-level PM2.5 measurements were performed in winter and summer, respectively. The inflammatory marker (high-sensitivity C-reactive protein, hs-CRP), immune parameters (IgA, IgG, IgM and IgE) and lymphocyte profiles (CD4 T cells, CD8 T cells, CD4/CD8 T cells) were measured in blood. The associations between individual-level PM2.5 and inflammatory marker and immune parameters were analysed by multiple linear regression. Results The average concentration of 24 h personal PM2.5 for participants was 116.98 μg/m3 and 86.48 μg/m3 in winter and summer, respectively. In the main analysis, PM2.5 exposure is associated with the increases in hs-CRP of 1.1%, IgG of 6.7%, IgM of 11.2% and IgE of 3.3% in participants, and decreases in IgA of 4.7% and CD8 of 0.7%, whereas we found no statistical association in CD4 T cells and CD4/CD8 T cells. In the adjusted model, the results showed that the increase of PM2.5 was associated with the changes of inflammatory markers and immune markers both in winter and summer. Conclusions Traffic policeman have been a high-risk group suffering inflammatory response or immune injury because of the high exposure to PM2.5. These findings provided new insight into the mechanisms linking ambient PM2.5 and inflammatory and immune response.

Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells.

Although the mechanisms linking cardiopulmonary diseases to ambient fine particles (PM2.5) are still unclear, inflammation and oxidative stress play important roles in PM2.5-induced injury. It is well known that inflammation and oxidative stress could be restricted by vitamin E (Ve) or omega-3 fatty acids (Ω-3 FA) consumption. This study investigated the effects of Ve and Ω-3 FA on PM2.5-induced inflammation and oxidative stress in vascular endothelial cells. The underlying mechanisms linking PM2.5 to vascular endothelial injury were also explored. Human umbilical vein endothelial cells (HUVECs) were treated with 50 μg/mL PM2.5 in the presence or absence of different concentrations of Ve and Ω-3 FA. The inflammatory cytokines and oxidative stress markers were determined. The results showed that Ve induced a significant decrease in PM2.5-induced inflammation and oxidative stress. Malondialdehyde (MDA) in supernatant and reactive oxygen species (ROS) in cytoplasm decreased by Ve, while the superoxide dismutase (SOD) activity elevated. The inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) also reduced by Ve. Moreover, Ω-3 FA played the same role on decreasing the inflammation and oxidative stress. IL-6 and TNF-α expressions were significantly lower in combined Ve with Ω-3 FA than treatment with Ve or Ω-3 FA alone. The Ve and Ω-3 FA intervention might abolish the PM2.5-induced oxidative stress and inflammation in vascular endothelial cells. There might be an additive effect of these two nutrients in mediating the PM2.5-induced injury in vascular endothelial cells. The results suggested that inflammation and oxidative stress might be parts of the mechanisms linking PM2.5 to vascular endothelial injury.

Preexposure to PM2.5 exacerbates acute viral myocarditis associated with Th17 cell.

BACKGROUND It is increasingly recognized that exposure to ambient fine particles (PM(2.5)) is a risk factor for the development of cardiovascular events. This study was to explore the link between PM(2.5) exposure and viral myocarditis in the functional mechanism of Th17 cells. METHODS Male BALB/c mice were administered an intratracheal (i.t.) instillation of 10 mg/kg b.w. PM(2.5) particles. Twenty-four hours later, the mice were injected intraperitoneally (i.p.) with 100 μl of coxsackievirus B3 (CVB3) diluted in Eagles minimal essential medium (EMEM). Seven days after the treatment, pulmonary and cardiac tissues were examined. RESULTS The results showed that preexposure to PM(2.5) increased the cardiac and pulmonary injuries and viral replication in the heart of CVB3-infected mice along with an increase in CD4(+) IL-17(+) cells in the spleen and heart. The mRNA expressions of interleukin-17A (IL-17A), perforin, transforming growth factor-β (TGF-β) and RORγt were up-regulated in PM(2.5)-pretreated mice than that in the virus-treated mice. Additionally, compared to virus-treated mice, the cardiac protein expressions of IL-17A and matrix metalloproteinases-2 (MMP-2) were increased, but interferon-γ (IFN-γ) and metalloproteinases-1 (TIMP-1) were decreased in PM(2.5)-pretreated mice. Interestingly, PM(2.5) caused IFN-γ decreased, whereas CVB3 caused a dramatic increase in IFN-γ. Subsequently, preexposure to PM(2.5) induced a slight increase of IFN-γ in the sera of CVB3-infected mice. CONCLUSIONS These results demonstrated that PM(2.5) exposure exacerbated virus-induced myocarditis possibly through the increase in Th17-mediated viral replication, perforin response and imbalance of MMP-2/TIMP-1. These findings provided supportive evidence for the epidemiological research that ambient particles could increase the occurrence and development of cardiovascular diseases.

Association between individual PM2.5 exposure and DNA damage in traffic policemen.

Objective: The aim of this study was to explore the association between individual PM2.5 and DNA damage in traffic policemen. Methods: The participants included 110 traffic policemen and 101 common populations. The continuous 24-hour individual PM2.5 measurement was performed in participants. BPDE (benzo[a]pyrene 7,8-diol-9,10-epoxide)-DNA adducts and 1-OHP were detected. Results: The average concentration of 24-hour personal PM2.5 for traffic policemen was significantly higher than that in the control group. PM2.5 exposure is associated with a 1.1% increase in 1-OHP and 0.8% increase in BPDE-DNA adducts after adjusted for body mass index, educational time period, and alcohol intake. Exposure group has 2.04 times higher of 1-OHP and 1.25 times higher of BPDE-DNA adducts when compared to the control group. Conclusions: These results demonstrated that traffic policemen have been a high-risk group suffering DNA damage because of the high PM2.5 exposure.

Combined effects of vitamin E and omega-3 fatty acids on protecting ambient PM2.5-induced cardiovascular injury in rats

OBJECTIVE This study aims to observe whether the combined treatment with vitamin E (vit E) and omega-3 polyunsaturated fatty acids (Ω-3 FA) could prevent the fine particulate matter (PM2.5)-induced cardiovascular injury through alleviating inflammation and oxidative stress. At the same time, the appropriate combination dosage of vit E and Ω-3 FA was explored to find an optimized protective dose to protect the injury induced by PM2.5. METHODS The SD rats were pretreated with different concentration of vit E and Ω-3 FA separately or jointly. Then the rats were exposed to ambient PM2.5 by intratracheal instillation for three times. The expression of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in serum and supernatant of cardiac tissue were detected by ELISA kits. The levels of malondialdehyde (MDA), superoxide Dismutase (SOD) and glutathione-peroxidase (GSH-Px) in myocardium and the level of MDA in serum were measured. Meanwhile, the cardiac injury was evaluated by histopathological examination. RESULTS Compared with the severe injury of rats in PM2.5 exposure group, the rats in vit E or Ω-3 FA-pretreated groups had a slighter injury in heart. Meanwhile, pretreatment with vit E or Ω-3 FA induced a significantly alleviation of the inflammatory cytokines (TNF-α, IL-1β, IL-6) and the elevation of the anti-oxidative activity especially in the rats pretreated with combined vit E and Ω-3 FA. In addition, the combined protecting effects of vit E and Ω-3 FA showed a dose-dependent manner. CONCLUSION Supplementation with vit E and Ω-3 FA could protect the PM2.5-induced injury, and the combination of vit E and Ω-3 FA might produce more effective effects than the separate nutrient did.

Air pollution is associated with the development of atherosclerosis via the cooperation of CD36 and NLRP3 inflammasome in ApoE-/- mice

Previous studies have indicated that the main air pollutant fine particulate matter (≤2.5 μm; PM2.5) exposure is associated with the development of atherosclerosis. Although the mechanism is not fully illustrated, the inflammatory responses play an important role. The present study aimed to explore whether PM2.5-exacerbated atherosclerosis was mediated by the cooperation of cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E-/- (ApoE-/-) mice. Thirty-two ApoE-/- mice were randomly divided into two groups. One group was fed with high fat chow (HFC) for 10 weeks to establish atherosclerotic model, and the other was fed with normal chow (NC). From week 11, the mice were exposed to concentrated PM2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linkixposed to concentrated PM2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linking air pollution and HFC-induced atherosclerosis even in the mice with NC intake.

CARD9-mediated ambient PM2.5-induced pulmonary injury is associated with Th17 cell

Inflammation and oxidative stress are important risk factors in PM2.5-induced injury. The current study attempted to study the role of caspase recruitment domain (CARD) 9 in ambient PM2.5-induced pulmonary injury in mice. The CARD9-/- and C57BL/6 mice were exposed to 3.6, 7.8 and 15.6mg/kgbw of PM2.5 or saline by intratracheal instillation. After the last PM2.5 exposure, the spleen, bronchoalveolar lavage fluid (BALF) and pulmonary tissue were collected and examined. The results showed that PM2.5 exposure induced inflammatory cell infiltration and alveolar septal thickening in the lung. Regulatory T (Treg) cells in spleen of CARD9-/- mice were significantly higher than that in the C57BL/6 mice, whereas the T helper cells 17 (Th17) were lower. The levels of interleukin (IL)-6 and IL-17A in BALF of the CARD9-/- mice were significantly lower than that in the C57BL/6 mice. The mRNA expression of IL-17A, IL-6 and RORγt in the lung of the CARD9-/- mice is significantly lower than that in the C57BL/6 mice, whereas the mRNA levels of Foxp3 in CARD9-/- mice were significantly higher than that in the C57BL/6 mice at the same dose of PM2.5. The protein expression of nuclear factor κB (NF-κB) is higher in the C57BL/6 mice than that in the CARD9-/- mice. This study indicates that ambient PM2.5-induced pulmonary injury is associated with the immune and inflammatory response. CARD9-mediated Th17/Treg differentiation probably played an important role in PM2.5-induced pulmonary damage.

The essential function of CARD9 in diet-induced inflammation and metabolic disorders in mice

Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)‐treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9−/− and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway‐related gene and protein were determined in insulin‐responsive organs using Western blotting and quantitative PCR. The results showed that HFD‐induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9−/− mice. CARD9 absence significantly modified O2 consumption, CO2 production and heat production. CARD9−/− mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD‐ and ND‐treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9−/− mice. The results indicated that CARD9 absence could be a vital protective factor in diet‐induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet‐induced obesity and metabolism disorder.

The severity of lung injury and metabolic disorders induced by ambient PM2.5 exposure is associated with cumulative dose

Abstract Lots of epidemiological and experimental studies have found that ambient fine particulate matter (PM2.5) exposure is associated with the development of cardiopulmonary diseases, obesity and diabetes. This study focused on the effects of cumulative PM2.5 exposure on pulmonary and systemic inflammation and insulin resistance. Thirty-two 6-week-old male Balb/c mice were randomly divided into four groups (FA, PM, WEEK and DAY groups) and were continuously or intermittently exposed to concentrated PM2.5 or filtered air (FA) for four weeks using Shanghai Meteorological and Environmental Animal Exposure System (“Shanghai-METAS”). The levels of IL-6 and TNF-α in serum, bronchoalveolar lavage fluid (BALF), lung tissues and white adipose tissue (WAT) were measured. Meanwhile, the expression of NF-κB and phosphor-NF-κB in lung tissue was detected by Western blot. Glucose tolerance and insulin resistance were also determined at the end of exposure. The results found that the mice in PM group displayed moderate inflammatory cell infiltration in lung, whereas the mice in WEEK and DAY groups displayed slight inflammatory cell infiltration in lung. Compared with the mice in FA group, the mRNA expressions of IL-6 and TNF-α in lung tissue and WAT significantly increased in the mice of PM group. Importantly, IL-6 and TNF-α mRNA expressions in PM group were higher than those in WEEK and DAY groups. The protein expression of phospho-NF-κB in lung tissue showed that PM group showed the activation of NF-κB, which was higher than that in the WEEK and DAY groups. Meanwhile, the mice in PM group showed more severe glucose tolerance and insulin resistance than that in the WEEK and DAY groups. The results suggested that the reduction of PM2.5 cumulative exposure may alleviate pulmonary and adipose inflammation, insulin resistance and glucose tolerance impairment. The results provided a clue that the interruption of ambient PM2.5 exposures by systems such as indoor air purification could be of benefit to people’s health.