PMID: 

Sci Rep. 2017 03 9 ;7:44256. Epub 2017 Mar 9. PMID: 28276511

Abstract Title: 

The acute airway inflammation induced by PMexposure and the treatment of essential oils in Balb/c mice.

Abstract: 

PMis the main particulate air pollutant whose aerodynamic diameter is less than 2.5 micron. The inflammation of various respiratory diseases are associated with PMinhalation. Pro-inflammatory cytokine IL-1β generated from effected cells usually plays a crucial role in many kinds of lung inflammatory reactions. The exacerbation of Th immune responses are identified in some PMrelated diseases. To elucidate the underlying mechanism of PM-induced acute lung inflammation, we exposed Balb/c mice to PMintratracheally and established a mice model. Acute lung inflammation and increased IL-1β expression was observed after PMinstillation. Regulatory factors of IL-1β (TLR4/MyD88 signaling pathway and NLRP3 inflammasome) participated in this lung inflammatory response as well. Treatment with compound essential oils (CEOs) substantially attenuated PM-induced acute lung inflammation. The decreased IL-1β and Th immune responses after CEOs treatment were significant. PMmay increase the secretion of IL-1β through TLR4/MyD88 and NLRP3 pathway resulting in murine airway inflammation. CEOs could attenuate the lung inflammation by reducing IL-1β and Th immune responses in this model. This study describes a potentially important mechanism of PM-induced acute lung inflammation and that may bring about novel therapies for the inflammatory diseases associated with PMinhalation.

read more

PMID: 

Ecotoxicol Environ Saf. 2019 Oct 30 ;182:109425. Epub 2019 Jul 8. PMID: 31295660

Abstract Title: 

Resveratrol alleviates chronic"real-world"ambient particulate matter-induced lung inflammation and fibrosis by inhibiting NLRP3 inflammasome activation in mice.

Abstract: 

BACKGROUND: Inhalation offine particulate matter (PM) induces the occurrence of lung inflammation and fibrosis, but its molecular mechanism remains unclear. Resveratrol (RES) is known to have anti-inflammatory properties in many pulmonary diseases. Here, we aimed to investigate the effect of long-term"real-world"ambient PM exposure on lung inflammation and fibrosis and further explore the protective effect and mechanism of RES.METHODS AND RESULTS: RES (50 and 100 mg/kg.bw) was administered to C57BL/6J mice that were exposed to ambient PM for 5 months. The control group breathed filtered air without RES, and the PM group was exposed to PM without RES. The inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and lung fibrosis were evaluatedby enzyme-linked immune sorbent assay (ELISA) kits and Masson's trichrome staining. The real-time PCR and Western blot analysis were used to determine the signal pathway. In vivo, PM exposure markedly elevated the levels of inflammatory cytokines and TGF-β1 in BALF, induced lung fibrosis. Meanwhile, PM exposure triggered autophagy process and activated the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in lung. Also, RES treatment abolished PM-induced lung inflammation and fibrosis, and inhibited autophagic process and NLRP3 inflammasome activation. In vitro,PM-induced cytotoxicity in BEAS-2B cells dose-dependently. Besides, RES alleviated PM-induced cytotoxicity, inhibited autophagic process and NLRP3 inflammasome activity and decreased IL-1β production in BEAS-2B cells.CONCLUSION: Long-term PM exposure induced lung inflammation and fibrosis, and RES intervention alleviated these adverse effects via inhibiting autophagy-related NLRP3 inflammasome activation.

read more

PMID: 

Inhal Toxicol. 2018 05 ;30(6):239-246. Epub 2018 Sep 24. PMID: 30249144

Abstract Title: 

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

Abstract: 

Lots of epidemiological and experimental studies have found that ambient fine particulate matter (PM) exposure is associated with the development of cardiopulmonary diseases, obesity and diabetes. This study focused on the effects of cumulative PMexposure 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 PMor 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. Theresults 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 PMcumulative exposure may alleviate pulmonary and adipose inflammation, insulin resistance and glucose tolerance impairment. The results provided a clue that the interruption of ambient PMexposures by systems such as indoor air purification could be of benefit to people's health.

read more

PMID: 

Environ Sci Pollut Res Int. 2018 Dec ;25(34):34221-34227. Epub 2018 Oct 5. PMID: 30291606

Abstract Title: 

Chitosan oligosaccharides alleviate PM-induced lung inflammation in rats.

Abstract: 

Air pollution of particulate matter (PM), especially PM, has become a major public health problem in China. Exploration of therapeutic and preventive measures against PMtoxicity is of practical significance. The aim of this study was to examine the inhibitory effects of chitosan oligosaccharides (COS) on PM-induced lung inflammation in rats. Forty SPF (specific pathogen-free) male Wistar rats weighing 200-220 g were randomly divided into four groups: control group, COS group, PMgroup, and PM+COS group. COS was pre-administered to rats by gavage at a single dose of 500 mg/kg 2 h before intratracheal instillation of PMat a single dose of 1.2 mg/kg daily for 3 consecutive days. Normal saline (NS) was used as negative control. Twenty-four hours after the last instillation of PM, rats were sacrificed and subjected to bronchoalveolar lavage (BAL). The BAL fluids (BALF) were collected for measurement of levels of total proteins, lactate dehydrogenase (LDH), interleukin-1 (IL-1β), IL-8, and tumor necrosis factor-ɑ (TNF-ɑ) using colorimetric or ELISA kits. Levels of total proteins, LDH activities, and pro-inflammatory mediators including IL-1β, IL-8, and TNF-ɑ in BALF of rats in PMgroup significantly increased in comparison with those of the control group. Pre-treatment of rats with COS markedly blocked PM-induced increase in LDH, IL-8, and TNF-ɑ levels in BALF. In conclusion, PMexposure induces rat lung inflammation, which could be ameliorated by the pre-treatment of COS.

read more

PMID: 

Sci Total Environ. 2019 Feb 10 ;650(Pt 1):908-921. Epub 2018 Sep 7. PMID: 30308865

Abstract Title: 

PM-induced alteration of DNA methylation and RNA-transcription are associated with inflammatory response and lung injury.

Abstract: 

The mechanisms of systemic pulmonary inflammation and toxicity of fine particulate matter (PM) exposure remains unclear. The current study investigated the inflammatory response and lung toxicity of PMin rats following intratracheal instillation of PM. After repeated (treated every 3 days for 30 days) PMexposure, total protein (TP), lactate dehydrogenase (LDH) activity and inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) levels in bronchoalveolar lavage fluid (BALF) were markedly elevated. The expression levels of IL-6, IL-1β, TNF-α and NF-κB in rat lung tissue and BEAS-2B cells were significantly upregulated after PMexposure. Histopathological evaluation suggested that the major pathological changes were alveolar wall thickening and inflammatory cell infiltration of the lungs. Genome wide DNA methylation and RNA-transcription analysis was performed on human bronchial epithelial cells (BEAS-2B) to explore the potential mechanisms in vitro. PMinduced genome wide DNA methylation and transcription changes. Differentially methylated CpGs were located in gene promoter region linked with CpG islands. Integrated analysis with DNA methylation and transcription data indicated a clear bias toward transcriptional alteration by differential methylation. Disease ontology of differentially methylated and expressed genes addressed their prominent role in respiratory disease. Functional enrichment revealed their involvement in inflammation or immune response, cellular community, cellular motility, cell growth, development and differentiation, signal transduction and responses to exogenous stimuli. Gene expression validation of ACTN4, CXCL1, MARK2, ABR, PSEN1, PSMA3, PSMD1 verified their functional participation in critical biological processes and supported the microarray bioinformatics analysis. Collectively, our data shows that PMinduced genome wide methylome and transcriptome alterations that could be involved in pulmonary toxicity and pathological process of respiratory disease, providing new insight into the toxicity mechanisms of PM.

read more

PMID: 

Wei Sheng Yan Jiu. 2008 Jul ;37(4):423-8. PMID: 18839524

Abstract Title: 

[Study of ambient PM2.5 on the influence of the inflammation injury and the immune function of subchronic exposure rats].

Abstract: 

OBJECTIVE: To explore ambient PM2.5 the influence of the inflammation injury and the on immune function.METHODS: The model rats were administered with PM2.5 by the intratracheal instillation. The pathological varieties of rat's lungs and other important organs were observed by light microscope. The protein and SA levels in bronchoalveolar lavage fluids (BALF) were detected by relevant kits. The TNF-alpha, and IL-6 levels in the BALF were detected by ELISA, and the mRNA expression levels in the lung tissue were observed by RT-PCR. The AM were collected to detect the phogacytic function. The ConA-stimulated T lymphocyte proliferation tests were performed to research the proliferation of spleen.RESULTS: Foreign-body granulomas were observed in the lungs of exposed rats. Monocytes-macrophages assembling in blood sinus of liver and the trend to form the granulomas were observed. Alveolar macrophages containing PM2.5 and dissociative PM2.5 were obviously observed in lung visceral pleural lymphatics and the blood vessels in lung and kidney. The number of the granulomas in the lungs of the rats become more and more as times goes on. The concentrations of total protein and SA in BALF were increased with the dose and time of exposure. TNF-alpha levels in the BALF increased by the dose and exposure time during 3 months, but TNF-alpha levels in the BALF decreased significantly on the 6th month. The expression levels of IL-6 in the BALF increased by the dose. It showed the dose-response relationship. The highest expression level of IL-6 was detected on the 3rd month. The expression level of IL-6 decreased on the 6th month. Phagocytiosis functions of AM were impaired by PM2.5 , which may in turn impair the nonspecific defenses function of airway. But the splenic lymphocyte proliferation were not obviously changed.CONCLUSION: The persistent inflammatory injury was induced by the subchronic exposure to PM2.5. The injury of immunological system were increased with the dose and the time of the exposure. The cytokine net was disordered by PM2.5, which worsen the injury. The phagocytiosis function of AM was impaired by PM2.5, which may be the mechanism of chronic pulmonary diseases.

read more

PMID: 

Zhonghua Jie He He Hu Xi Za Zhi. 2013 Nov ;36(11):836-40. PMID: 24507396

Abstract Title: 

[Effects of PM2.5 exposure on Klebsiella pneumoniae clearance in the lungs of rats].

Abstract: 

OBJECTIVE: To investigate the effects of PM2.5 exposure on susceptibility to Klebsiella infection and bacterial clearance, and to discuss its possible mechanisms.METHODS: Eighty-six healthy male SD rats were randomly divided into 4 groups: a control group, a Klebsiella pneumoniae infection group(infection group), a PM2.5 group and a PM2.5+ Klebsiella pneumoniae infection group (combined group) .We developed a rat model in which the animals were given Klebsiella pneumoniae, PM2.5 exposure and PM2.5 exposure followed by infection with Klebsiella pneumoniae respectively. The clinical scores were evaluated. The total mortality of each group was assessed. Bacterial load in the BALF was quantified and the infection rate of each group was assessed.Lung histopathological changes were detected by HE staining. The concentrations of IL-6 and TNF-α in serum were detected by ELISA. Cells in the BALF were counted for each group by microscopy. The changes of tracheal membrane epithelial cells were observed by scanning electron microscope.RESULTS: The total mortality in the combined group (n = 14) was higher than that in the control group (n = 0), infection group(n = 4) and PM2.5 group(n = 4). The infected cases in the combined infection group (n = 13) was higher than that in the infection group (n = 6). The total number of WBC in BALF in the combined group on the first day[(11.96± 0.56)×10(5)/L] and seventh day [(15.68 ± 0.81)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The neutrophil number in BALF in the combined group on the first day[(5.76 ± 0.44)×10(5)/L] and seventh day [(9.41 ± 0.64)×10(5)/L] was higher than that in the control group, the infection group and the PM2.5 group. The lung pathological changes were much more severe in the combined group as compared to those in the control, the infection and the PM2.5 groups. Concentrations of TNF-α in serum in the combined group on the first day [(829 ± 90) ng/L] and the seventh day [(1055 ± 91) ng/L] were higher than those in the control group and the PM2.5 group. Concentrations of IL-6 in serum in the combined group on the first day [(1.26 ± 0.16) ng/L] and seventh day [(1.95 ± 0.18) ng/L] was higher than those in the control, the infection and thePM2.5 groups. Tracheal cilia in the PM2.5 group showed signs of disorderly arrangement, adhesion and ecclasis.CONCLUSIONS: PM2.5 exposure increased the susceptibility of the rats to Klebsiella pneumoniae infection and decreased bacterial clearance.Its mechanism may be related to impairment of the bronchial mucociliary system and interaction of cytokines.

read more

PMID: 

Toxicology. 2014 Nov 5 ;325:180-8. Epub 2014 Sep 16. PMID: 25220797

Abstract Title: 

Exposure to particular matter increases susceptibility to respiratory Staphylococcus aureus infection in rats via reducing pulmonary natural killer cells.

Abstract: 

Epidemiological studies have shown a correlation between exposure to fine particular matter (PM2.5) and increased respiratory infection, but the mechanisms have remained poorly defined. By using an experimental system we evaluated the effect of PM2.5 exposure on susceptibility to subsequent pulmonary Staphylococcus aureus (S. aureus) infection and its potential mechanisms. Rats were intratracheally instilled with a single dose of PM2.5 sample or PBS followed by an intratracheal inoculation with bacteria S. aureus at 24h after PM2.5 exposure. The rats were examined at 24h post infection. We found that exposure of rats to PM2.5 significantly increased inflammatory cells and levels of IL-6 and TNF-α in bronchoalveolar lavage fluids (BALF). Prior PM2.5 exposure markedly increased the susceptibility of rats to subsequent S. aureus infection. The mechanistic studies showed that alveolar macrophages (AMs) from PM2.5-experienced lungs had depressed phagocytosis of S. aureus, and prior PM2.5 exposure significantly decreased the natural killer (NK) cells recruited into the airways following subsequent S. aureus infection. Further, adoptive transfer of naive NK cells to the lung of prior PM2.5-exposed rats restored PM2.5-impaired antibacterial host defense. The presence of NK cells markedly enhanced the ability of AMs to phagocytose S. aureus ex vivo. Thus, our study identifies PM2.5-impaired NK cell response in the lung to be a novel critical mechanism for PM2.5-mediated susceptibility to S. aureus bacterial infection, which provides a potential mechanism to explain the epidemiologicalfindings that associate ambient air pollution and increased lung bacterial infections. Our findings also suggest that enhancing pulmonary NK cells may be considered for future therapeutic approaches to clinically antibiotic-resistant S. aureus infection in the lung.

read more

PMID: 

Environ Sci Technol. 2020 Jan 21 ;54(2):975-984. Epub 2019 Dec 18. PMID: 31755707

Abstract Title: 

Associations between Source-Specific Particulate Matter and Respiratory Infections in New York State Adults.

Abstract: 

The response of respiratory infections to source-specific particulate matter (PM) is an area of active research. Using source-specific PMconcentrations at six urban sites in New York State, a case-crossover design, and conditional logistic regression, we examined the association between source-specific PM and the rate of hospitalizations and emergency department (ED) visits for influenza or culture-negative pneumonia from 2005 to 2016. There were at most= 14 764 influenza hospitalizations,= 57 522 influenza ED visits,= 274 226 culture-negative pneumonia hospitalizations, and= 113 997 culture-negative pneumonia ED visits included in our analyses. We separately estimated the rate of respiratory infection associated with increased concentrations of source-specific PM, including secondary sulfate (SS), secondary nitrate (SN), biomass burning (BB), pyrolyzed organic carbon (OP), road dust (RD), residual oil (RO), diesel (DIE), and spark ignition vehicle emissions (GAS). Increased rates of ED visits for influenza were associated with interquartile range increases in concentrations of GAS (excess rate [ER] = 9.2%; 95% CI: 4.3%, 14.3%) and DIE (ER = 3.9%; 95% CI: 1.1%, 6.8%) for lag days 0-3. There were similar associations between BB, SS, OP, and RO, and ED visits or hospitalizations for influenza, but not culture-negative pneumonia hospitalizations or ED visits. Short-term increases in PMfrom traffic and other combustion sources appear to be a potential risk factor for increased rates of influenza hospitalizations and ED visits.

read more

PMID: 

PLoS One. 2011 ;6(6):e20827. Epub 2011 Jun 10. PMID: 21695220

Abstract Title: 

Long-term exposure to ambient air pollution and mortality due to cardiovascular disease and cerebrovascular disease in Shenyang, China.

Abstract: 

BACKGROUND: The relationship between ambient air pollution exposure and mortality of cardiovascular and cerebrovascular diseases in human is controversial, and there is little information about how exposures to ambient air pollution contribution to the mortality of cardiovascular and cerebrovascular diseases among Chinese. The aim of the present study was to examine whether exposure to ambient-air pollution increases the risk for cardiovascular and cerebrovascular disease.METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study among humans to examine the association between compound-air pollutants [particulate matter

read more