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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer’s disease

Authors: Bian-Rong Wang, Jian-Quan Shi, Nian-Nian Ge, Zhou Ou, You-Yong Tian, Teng Jiang, Jun-Shan Zhou, Jun Xu, Ying-Dong Zhang

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Numerous studies suggested that PM2.5 exposure was associated with increased risk of Alzheimer’s disease (AD). But the precise mechanisms by which PM2.5 contributed to AD pathogenesis have not been clarified.

Methods

In the presence or absence of neurons, oligomeric amyloid beta (oAβ)-primed microglia were stimulated with PM2.5. Firstly, we determined the effects of PM2.5 exposure on neuronal injury and inflammation in neurons-microglia co-cultures. Then, we examined whether NLRP3 inflammasome activation was involved in PM2.5-induced inflammation. After that, we investigated whether PM2.5 exposure increased ROS level in oAβ-stimulated microglia. At last, we examined whether ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures.

Results

In the present study, we showed that PM2.5 exposure aggravated oAβ-induced neuronal injury and inflammation in neurons-microglia co-cultures via increasing IL-1β production. Further, PM2.5-induced IL-1β production in oAβ-stimulated microglia was possibly dependent on NLRP3 inflammasome activation. Meanwhile, PM2.5 exposure increased ROS level in oAβ-stimulated microglia. ROS was required for PM2.5-induced IL-1β production and NLRP3 inflammasome activation in oAβ-stimulated microglia. More importantly, ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures.

Conclusions

For the first time, these results suggested that the effects of PM2.5 under AD context were possibly mediated by NLRP3 inflammasome activation, which was triggered by ROS. Taken together, these findings have deepened our understanding on the role of PM2.5 in AD pathogenesis.
Literature
1.
2.
3.
Yegambaram M, Manivannan B, Beach TG, Halden RU. Role of environmental contaminants in the etiology of Alzheimer’s disease: a review. Curr Alzheimer Res. 2015;12:116–46.CrossRefPubMed
4.
Craig L, Brook JR, Chiotti Q, Croes B, Gower S, Hedley A, et al. Air pollution and public health: a guidance document for risk managers. J Toxicol Environ Health A. 2008;71:588–698.CrossRefPubMed
5.
Jung CR, Lin YT, Hwang BF. Ozone, particulate matter, and newly diagnosed Alzheimer’s disease: a population-based cohort study in Taiwan. J Alzheimers Dis. 2015;44:573–84.PubMed
6.
Spangenberg EE, Green KN. Inflammation in Alzheimer’s disease: lessons learned from microglia-depletion models. Brain Behav Immun. 2017;61:1–11.CrossRefPubMed
7.
Calderón-Garcidueñas L, Calderón-Garcidueñas A, Torres-Jardón R, Avila-Ramírez J, Kulesza RJ, Angiulli AD. Air pollution and your brain: what do you need to know right now. Prim Health Care Res Dev. 2015;16:329–45.CrossRefPubMed
8.
Campbell A, Oldham M, Becaria A, Bondy SC, Meacher D, Sioutas C, et al. Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology. 2005;26:133–40.CrossRefPubMed
9.
Campbell A, Araujo JA, Li H, Sioutas C, Kleinman M. Particulate matter induced enhancement of inflammatory markers in the brains of apolipoprotein E knockout mice. J Nanosci Nanotechnol. 2009;9:5099–104.CrossRefPubMed
10.
Guerra R, Vera-Aguilar E, Uribe-Ramirez M, Gookin G, Camacho J, Osornio-Vargas AR, et al. Exposure to inhaled particulate matter activates early markers of oxidative stress, inflammation andunfolded protein response in rat striatum. Toxicol Lett. 2013;222:146–54.CrossRefPubMedPubMedCentral
11.
Ying Z, Xu X, Bai Y, Zhong J, Chen M, Liang Y, et al. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation. Environ Health Perspect. 2014;122:79–86.PubMed
12.
Bhatt DP, Puig KL, Gorr MW, Wold LE, Combs CK. A pilot study to assess effects of long-term inhalation of airborne particulate matter on early Alzheimer-like changes in the mouse brain. PLoS One. 2015;10:e0127102.CrossRefPubMedPubMedCentral
13.
14.
Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–65.CrossRefPubMedPubMedCentral
15.
Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493:674–8.CrossRefPubMed
16.
White CS, Lawrence CB, Brough D, Rivers-Auty J. Inflammasomes as therapeutic targets for Alzheimer’s disease. Brain Pathol. 2017;27:223–2234.CrossRefPubMed
17.
Hirota JA, Hirota SA, Warner SM, Stefanowicz D, Shaheen F, Beck PL, et al. The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter. J Allergy Clin Immunol. 2012;129:1116–25.CrossRefPubMed
18.
Hirota JA, Gold MJ, Hiebert PR, Parkinson LG, Wee T, Smith D, et al. The nucleotide-binding domain, leucine-rich repeat protein 3 inflammasome/IL-1 receptor I axis mediates innate, but not adaptive, immune responses after exposure to particulate matter under 10 μm. Am J Respir Cell Mol Biol. 2015;52:96–105.CrossRefPubMed
19.
Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, et al. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron. 2013;78:631–43.CrossRefPubMedPubMedCentral
20.
Mizuno T, Kurotani T, Komatsu Y, Kawanokuchi J, Kato H, Mitsuma N, Suzumura A. Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia. Neuropharmacology. 2004;46:404–11.CrossRefPubMed
21.
Doi Y, Mizuno T, Maki Y, Jin S, Mizoguchi H, Ikeyama M, et al. Microglia activated with the toll-like receptor 9 ligand CpG attenuate oligomeric amyloid {beta} neurotoxicity in in vitro and in vivo models of Alzheimer’s disease. Am J Pathol. 2009;175:2121–32.CrossRefPubMedPubMedCentral
22.
Parajuli B, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A. Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer’s disease. Cell Death Dis. 2013;4:e975.CrossRefPubMedPubMedCentral
23.
Shi JQ, Chen J, Wang BR, Zhu YW, Xu Y, Wang J, et al. Short amyloid-beta immunogens show strong immunogenicity and avoid stimulating pro-inflammatory pathways in bone marrow-derived dendritic cells from C57BL/6J mice in vitro. Peptides. 2011;32:1617–25.CrossRefPubMed
24.
Block ML, Wu X, Pei Z, Li G, Wang T, Qin L, et al. Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase. FASEB J. 2004;18(13):1618–20.CrossRefPubMed
25.
Shi JQ, Wang BR, Tian YY, Xu J, Gao L, Zhao SL, et al. Antiepileptics topiramate and levetiracetam alleviate behavioral deficits and reduce neuropathology in APPswe/PS1dE9 transgenic mice. CNS Neurosci Ther. 2013;19:871–81.CrossRefPubMed
26.
Liu D, Gao L, Roy SK, Cornish KG, Zucker IH. Role of oxidant stress on AT1 receptor expression in neurons of rabbits with heart failure and in cultured neurons. Circ Res. 2008;103:186–93.CrossRefPubMedPubMedCentral
27.
Wei H, Feng Y, Liang F, Cheng W, Wu X, Zhou R, et al. Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter. Toxicology. 2017;380:94–103.CrossRefPubMed
28.
Chen M, Li B, Sang N. Particulate matter (PM2.5) exposure season-dependently induces neuronal apoptosis and synaptic injuries. J Environ Sci (China). 2017;54:336–45.CrossRef
29.
Zhao Q, Chen H, Yang T, Rui W, Liu F, Zhang F, et al. Direct effects of airborne PM2.5 exposure on macrophage polarizations. Biochim Biophys Acta. 2016;1860:2835–43.CrossRefPubMed
30.
Grail A, Norval M. Significance of smoking and detection of serum antibodies to cytomegalovirus in cervical dysplasia. Br J Obstet Gynaecol. 1988;95:1103–10.CrossRefPubMed
31.
Zhang Y, Zheng L, Tuo J, Liu Q, Zhang X, Xu Z, et al. Analysis of PM2.5-induced cytotoxicity in human HaCaT cells based on a microfluidic system. Toxicol in Vitro. 2017;43:1–8.CrossRefPubMed
32.
Dong Y, Kalueff AV, Song C. N-methyl-d-aspartate receptor-mediated calcium overload and endoplasmic reticulum stress are involved in interleukin-1beta-induced neuronal apoptosis in rat hippocampus. J Neuroimmunol. 2017;307:7–13.CrossRefPubMed
33.
Song L, Pei L, Yao S, Wu Y, Shang Y. NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci. 2017;11:63.PubMedPubMedCentral
34.
35.
Piccini A, Carta S, Tassi S, Lasiglié D, Fossati G, Rubartelli A. ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc Natl Acad Sci USA. 2008;105:8067–872.CrossRefPubMedPubMedCentral
36.
Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, van der Meer JH, et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 2009;113:2324–35.CrossRefPubMedPubMedCentral
37.
Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117–21.CrossRefPubMed
38.
Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, et al. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015;4:296–307.CrossRefPubMedPubMedCentral
39.
Feng S, Gao D, Liao F, Zhou F, Wang X. The health effects of ambient PM2.5 and potential mechanisms. Ecotoxicol Environ Saf. 2016;128:67–74.CrossRefPubMed
40.
Fiordelisi A, Piscitelli P, Trimarco B, Coscioni E, Iaccarino G, Sorriento D. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail Rev. 2017;22:337–47.CrossRefPubMed
41.
Kim HJ, Choi MG, Park MK, Seo YR. Predictive and prognostic biomarkers of respiratory diseases due to particulate matter exposure. J Cancer Prev. 2017;22:6–15.CrossRefPubMedPubMedCentral
42.
Lee PC, Raaschou-Nielsen O, Lill CM, Bertram L, Sinsheimer JS, Hansen J, et al. Gene-environment interactions linking air pollution and inflammation in Parkinson’s disease. Environ Res. 2016;151:713–20.CrossRefPubMed
43.
Jin X, Su R, Li R, Song L, Chen M, Cheng L, et al. Amelioration of particulate matter-induced oxidative damage by vitamin c and quercetin in human bronchial epithelial cells. Chemosphere. 2016;144:459–66.CrossRefPubMed
44.
Jin XT, Chen ML, Li RJ, An Q, Song L, Zhao Y, et al. Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure. Arch Toxicol. 2016;90:1929–38.CrossRefPubMed
Metadata
Title
PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer’s disease
Authors
Bian-Rong Wang
Jian-Quan Shi
Nian-Nian Ge
Zhou Ou
You-Yong Tian
Teng Jiang
Jun-Shan Zhou
Jun Xu
Ying-Dong Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1178-5

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