Fine particulate matter-induced cardiovascular injury is associated with NLRP3 inflammasome activation in Apo E-/- mice

As one of the most harmful air pollutants, fine particulate matter (PM2.5) has been implicated as a risk factor for multiple diseases, which has generated widespread public concern. Accordingly, a growing literature links PM2.5 exposure with Alzheimer’s disease (AD). A critical gap in our understanding of the adverse effects of PM2.5 on AD is the mechanism triggered by PM2.5 that contributes to disease progression. Recent evidence has demonstrated that PM2.5 can activate NLRP3 inflammasome-mediated neuroinflammation. In this review, we highlight the novel evidence between PM2.5 exposure and AD incidence, which is collected and summarized from neuropathological, epidemiological, and neuroimaging studies to in-depth deciphering molecular mechanisms. First, neuropathological, epidemiological, and neuroimaging studies will be summarized. Then, the transport pathway for central nervous system delivery of PM2.5 will be presented. Finally, the role of NLRP3 inflammasome-mediated neuroinflammation in PM2.5 induced-effects on AD will be recapitulated.

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NLRP3 Inflammasome: A Potential Therapeutic Target in Fine Particulate Matter-Induced Neuroinflammation in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-200359 ◽

2020 ◽

Vol 77 (3) ◽

pp. 923-934

Author(s):

Jian-Quan Shi ◽

Bian-Rong Wang ◽

Teng Jiang ◽

Li Gao ◽

Ying-Dong Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Particulate Matter ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Fine Particulate Matter ◽

Transport Pathway ◽

Critical Gap ◽

Fine Particulate ◽

Pm2.5 Exposure

As one of the most harmful air pollutants, fine particulate matter (PM2.5) has been implicated as a risk factor for multiple diseases, which has generated widespread public concern. Accordingly, a growing literature links PM2.5 exposure with Alzheimer’s disease (AD). A critical gap in our understanding of the adverse effects of PM2.5 on AD is the mechanism triggered by PM2.5 that contributes to disease progression. Recent evidence has demonstrated that PM2.5 can activate NLRP3 inflammasome-mediated neuroinflammation. In this review, we highlight the novel evidence between PM2.5 exposure and AD incidence, which is collected and summarized from neuropathological, epidemiological, and neuroimaging studies to in-depth deciphering molecular mechanisms. First, neuropathological, epidemiological, and neuroimaging studies will be summarized. Then, the transport pathway for central nervous system delivery of PM2.5 will be presented. Finally, the role of NLRP3 inflammasome-mediated neuroinflammation in PM2.5 induced-effects on AD will be recapitulated.

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Carbon monoxide releasing molecule-2 protects against particulate matter-induced lung inflammation by inhibiting TLR2 and 4/ROS/NLRP3 inflammasome activation

Molecular Immunology ◽

10.1016/j.molimm.2019.05.005 ◽

2019 ◽

Vol 112 ◽

pp. 163-174 ◽

Cited By ~ 10

Author(s):

Chiang-Wen Lee ◽

Miao-Ching Chi ◽

Lee-Fen Hsu ◽

Chuen-Mao Yang ◽

Tsui-Hua Hsu ◽

...

Keyword(s):

Carbon Monoxide ◽

Particulate Matter ◽

Nlrp3 Inflammasome ◽

Lung Inflammation ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation

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Use of a Mechanism-based Toxicological Approach to Analyze the Pulmonary Pro-Fibrogenic Effects of Air Pollution PM2.5 Particulates

10.21203/rs.2.22194/v1 ◽

2020 ◽

Author(s):

Wei Cao ◽

Xiang Wang ◽

Ming Yan ◽

Chong Hyun Chang ◽

Joshua Kim ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Fine Particulate Matter ◽

Lung Epithelial Cells ◽

Chronic Obstructive ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation ◽

Oropharyngeal Aspiration ◽

Tgf Β1

Abstract Background Airborne fine particulate matter (PM2.5) has been known capable of causing acute and chronic respiratory inflammation such as chronic obstructive pulmonary disease (COPD) and lung fibrosis. With incremental experience in the predictive toxicological approach on the potential adverse effects of nanomaterials, it is logical to explore the feasibility of using such a mechanism-based approach on PM2.5-induced lung toxicity. Results In this study, we collected a panel of eight PM2.5 samples for a comparative analysis of their pro-fibrogenic effects in the lung. These samples were collected on filters in November 2017 in Zhengzhou, Henan, China. In vitro screening shows although the PM2.5 particles did not induce significant cytotoxicity, they cause potent TNF-α and interleukin-1β (IL-1β) production in THP-1 cells as well as TGF-β1 in BEAS-2B lung epithelial cells. PM2.5 induced IL-1β production was shown to involve NLRP3 inflammasome activation, which was evidenced by the inhibited IL-1β production in NLRP3- and ASC-deficient cells and use of an inhibitor for cathepsin B, a known activation of the inflammasome through lysosomal damage pathway. Administration of PM2.5 to the lung in mice via oropharyngeal aspiration confirmed that the particles could induce TGF-β1 production in the bronchoalveolar lavage (BAL) fluid and collagen deposition in the lung at 21 days post-exposure, suggesting PM2.5 has the potential to induce pulmonary fibrosis. The ranking of the pro-fibrogenic effects by the PM2.5 samples in vivo was consistent with that of the IL-1β production in vitro. Conclusions In summary, we demonstrate that the PM2.5 is capable of inducing NLRP3 inflammasome activation and a series of cellular responses originating from the epithelial–mesenchymal trophic cell unit in the lung to induce fibrosis in vivo.

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