scholarly journals Silicon Dioxide Nanoparticles Enhance Endotoxin-Induced Lung Injury in Mice

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2247 ◽  
Author(s):  
Je-Won Ko ◽  
Hae-Jun Lee ◽  
Na-Rae Shin ◽  
Yun-Soo Seo ◽  
Sung-Ho Kim ◽  
...  
Keyword(s):  
Silicon Dioxide ◽  
Inflammatory Responses ◽  
Metal Oxide Nanoparticles ◽  
Disease Model ◽  
Lavage Fluid ◽  
Silicon Dioxide Nanoparticles ◽  
Mapk Phosphorylation ◽  
Cell Counts ◽  
Mitogen Activated Protein ◽  
Intranasal Instillation

Silicon dioxide nanoparticles (SiONPs), which are metal oxide nanoparticles, have been used in a wide variety of applications. In this study, acute pulmonary responses were examined after the intranasal instillation of SiONPs in mice primed with or without lipopolysaccharide (LPS, intranasal, 5 µg/mouse). The exposure to SiONPs increased the inflammatory cell counts and proinflammatory cytokines in the bronchoalveolar lavage fluid. SiONPs induced airway inflammation with increases in the phosphorylation of mitogen-activated protein kinases (MAPKs). The ratios of the inflammatory responses induced by the SiONPs were increased in the acute pulmonary disease model primed by LPS. Taken together, SiONPs exhibited toxicity to the respiratory system, which was associated with MAPK phosphorylation. In addition, the exposure to SiONPs exacerbated any existing inflammatory pulmonary diseases. These data showed the additive, as well as synergistic, interaction effects of SiONPs and LPS. We conclude that the exposure to SiONPs causes potential toxicity in humans, especially those with respiratory diseases.

scholarly journals The combined effects of silicon dioxide nanoparticles and cold air exposure on the metabolism and inflammatory responses in white adipocytes

2017 ◽  
Vol 6 (5) ◽  
pp. 705-710
Author(s):  
Yongqiang Zhang ◽  
Xi Li ◽  
Yangsheng Lin ◽  
Li Zhang ◽  
Zhan Guo ◽  
...  
Keyword(s):  
Air Pollution ◽  
Silicon Dioxide ◽  
Inflammatory Responses ◽  
Potential Hazard ◽  
Combined Effects ◽  
Silicon Dioxide Nanoparticles ◽  
Air Exposure ◽  
Cold Air ◽  
White Adipocytes

The potential hazard of nanoparticles (NPs) from air pollution has attracted widespread attention.

Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice

2004 ◽  
Vol 287 (5) ◽  
pp. L944-L952 ◽  
Author(s):  
Anna M. van Heeckeren ◽  
Mark D. Schluchter ◽  
Mitchell L. Drumm ◽  
Pamela B. Davis
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Lung Infection ◽  
Agarose Beads ◽  
Cell Counts ◽  
Inflammatory Protein ◽  
Functional Defect ◽  
Infection And Inflammation

Patients with cystic fibrosis have a lesion in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which is associated with abnormal regulation of other ion channels, abnormal glycosylation of secreted and cell surface molecules, and vulnerability to bacterial infection and inflammation in the lung usually leading to the death of these patients. The exact mechanism(s) by which mutation in CFTR leads to lung infection and inflammation is not clear. Mice bearing different mutations in the murine homolog to CFTR ( Cftr) (R117H, S489X, Y122X, and ΔF508, all backcrossed to the C57BL/6J background) were compared with respect to growth and in their ability to respond to lung infection elicited with Pseudomonas aeruginosa-laden agarose beads. Body weights of mice bearing mutations in Cftr were significantly smaller than wild-type mice at most ages. The inflammatory responses to P. aeruginosa-laden agarose beads were comparable in mice of all four Cftr mutant genotypes with respect to absolute and relative cell counts in bronchoalveolar lavage fluid, and cytokine levels (TNF-α, IL-1β, IL-6, macrophage inflammatory protein-2, and keratinocyte chemoattractant) and eicosanoid levels (PGE2 and LTB4) in epithelial lining fluid: the few small differences observed occurred only between cystic fibrosis mice bearing the S489X mutation and those bearing the knockout mutation Y122X. Thus we cannot implicate either misprocessing of CFTR or failure of CFTR to reach the plasma membrane in the genesis of the excess inflammatory response of CF mice. Therefore, it appears that any functional defect in CFTR produces comparable inflammatory responses to lung infections with P. aeruginosa.

Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3455-3464 ◽  
Author(s):  
Richard A. Dean ◽  
Jennifer H. Cox ◽  
Caroline L. Bellac ◽  
Alain Doucet ◽  
Amanda E. Starr ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Binding Motif ◽  
Wild Type ◽  
Lps Challenge ◽  
Inflammatory Protein ◽  
Leukocyte Influx ◽  
Cc Chemokines ◽  
Intranasal Instillation

AbstractThrough the activity of macrophage-specific matrix metalloproteinase-12 (MMP-12), we found that macrophages dampen the lipopolysaccharide (LPS)-induced influx of polymorphonuclear leukocytes (PMNs)—thus providing a new mechanism for the termination of PMN recruitment in acute inflammation. MMP-12 specifically cleaves human ELR+ CXC chemokines (CXCL1, -2, -3, -5, and -8) at E-LR, the critical receptor-binding motif or, for CXCL6, carboxyl-terminal to it. Murine (m) MMP-12 also cleaves mCXCL1, -2, and -3 at E-LR. MMP-12-cleaved mCXCL2 (macrophage-inflammatory protein-2 [MIP-2]) and mCXCL3 (dendritic cell inflammatory protein-1 [DCIP-1]) lost chemotactic activity. Furthermore, MMP-12 processed and inactivated monocyte chemotactic proteins CCL2, -7, -8, and -13 at position 4-5 generating CCR antagonists. Indeed, PMNs and macrophages in bronchoalveolar lavage fluid were significantly increased 72 hours after intranasal instillation of LPS in Mmp12−/− mice compared with wild type. Specificity occurred at 2 levels. Macrophage MMP-1 and MMP-9 did not cleave in the ELR motif. Second, unlike human ELR+CXC chemokines, mCXCL5 (LPS-induced CXC chemokine [LIX]) was not inactivated. Rather, mMMP-12 cleavage at Ser4-Val5 activated the chemokine, promoting enhanced PMN early infiltration in wild-type mice compared with Mmp12−/− mice 8 hours after LPS challenge in air pouches. We propose that the macrophage, specifically through MMP-12, assists in orchestrating the regulation of acute inflammatory responses by precise proteolysis of ELR+CXC and CC chemokines.

Fine Particulate Matter and Sulfur Dioxide Coexposures Induce Rat Lung Pathological Injury and Inflammatory Responses Via TLR4/p38/NF-κB Pathway

2016 ◽  
Vol 36 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Ruijin Li ◽  
Lifang Zhao ◽  
Jinlong Tong ◽  
Yuchao Yan ◽  
Chong Xu
Keyword(s):  
Particulate Matter ◽  
Sulfur Dioxide ◽  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Fine Particulate Matter ◽  
Lavage Fluid ◽  
Cell Counts ◽  
Fine Particulate ◽  
Rat Lungs ◽  
Ultrastructural Damage

Fine particulate matter (PM2.5) and sulfur dioxide (SO2) are 2 common air pollutants, but their toxicological effects of coexposure are still not fully clear. In this study, SO2 exposure (5.6 mg/m3) couldn’t cause obvious inflammatory responses in rat lungs. The PM2.5 exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO2 and PM2.5 (1.5, 6.0, and 24.0 mg/kg) coexposure induced pathological and ultrastructural damage and raised inflammatory cells in BALF compared with the control. Also, they significantly elevated the levels of pro-inflammatory cytokines, adhesion molecule, and nitric oxide (NO) and promoted the gene expression of nuclear factor kappa B (NF-κB), phosphorylated p38 (p-p38), and Toll-like receptor 4 (TLR4) in rat lungs treated with higher dose of PM2.5 (6.0 and 24.0 mg/kg) plus SO2 relative to the control or SO2 group, along with the decreased inhibitor of NF-κBα and increased inhibitor of NF-κB kinase β expressions. The changes in the inflammatory markers in the presence of PM2.5 plus SO2 were not significant compared with the PM2.5 group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM2.5 plus SO2 were involved in TLR4/p38/NF-κB pathway activation accompanied by oversecretion of pro-inflammatory cytokine, adhesion molecule, and NO. It provides more useful evidence to understand the possible toxicological mechanism that PM2.5 and SO2 copollution exacerbate lung disease.

Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-κB, MAPK and Inflammatory Cytokines

2018 ◽  
Vol 46 (03) ◽  
pp. 651-671 ◽  
Author(s):  
Heng-Yuan Chang ◽  
Yi-Chuan Chen ◽  
Jaung-Geng Lin ◽  
I-Hsin Lin ◽  
Hui-Fen Huang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Oxidative Enzymes ◽  
Mitogen Activated Protein Kinases ◽  
Cell Counts ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5–20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.

scholarly journals Silicon dioxide nanoparticles induced neurobehavioral impairments by disrupting microbiota–gut–brain axis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jun Diao ◽  
Yinyin Xia ◽  
Xuejun Jiang ◽  
Jingfu Qiu ◽  
Shuqun Cheng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Health Risk ◽  
Silicon Dioxide ◽  
Spatial Learning And Memory ◽  
Rrna Gene ◽  
Silicon Dioxide Nanoparticles ◽  
Potential Health ◽  
Specific Chemical ◽  
Memory Impairments ◽  
Tissue Integrity

Abstract Background Silicon dioxide nanoparticles (SiO2NPs) are widely used as additive in the food industry with controversial health risk. Gut microbiota is a new and hot topic in the field of nanotoxicity. It also contributes a novel and insightful view to understand the potential health risk of food-grade SiO2NPs in children, who are susceptible to the toxic effects of nanoparticles. Methods In current study, the young mice were orally administrated with vehicle or SiO2NPs solution for 28 days. The effects of SiO2NPs on the gut microbiota were detected by 16S ribosomal RNA (rRNA) gene sequencing, and the neurobehavioral functions were evaluated by open field test and Morris water maze. The level of inflammation, tissue integrity of gut and the classical indicators involved in gut–brain, gut–liver and gut–lung axis were all assessed. Results Our results demonstrated that SiO2NPs significantly caused the spatial learning and memory impairments and locomotor inhibition. Although SiO2NPs did not trigger evident intestinal or neuronal inflammation, they remarkably damaged the tissue integrity. The microbial diversity within the gut was unexpectedly enhanced in SiO2NPs-treated mice, mainly manifested by the increased abundances of Firmicutes and Patescibacteria. Intriguingly, we demonstrated for the first time that the neurobehavioral impairments and brain damages induced by SiO2NPs might be distinctively associated with the disruption of gut–brain axis by specific chemical substances originated from gut, such as Vipr1 and Sstr2. Unapparent changes in liver or lung tissues further suggested the absence of gut–liver axis or gut–lung axis regulation upon oral SiO2NPs exposure. Conclusion This study provides a novel idea that the SiO2NPs induced neurotoxic effects may occur through distinctive gut–brain axis, showing no significant impact on either gut–lung axis or gut–liver axis. These findings raise the exciting prospect that maintenance and coordination of gastrointestinal functions may be critical for protection against the neurotoxicity of infant foodborne SiO2NPs.

scholarly journals Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation

2020 ◽  
Vol 6 (46) ◽  
pp. eabc1428
Author(s):  
A. Nakano-Kobayashi ◽  
A. Fukumoto ◽  
A. Morizane ◽  
D. T. Nguyen ◽  
T. M. Le ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Neuronal Survival ◽  
Disease Model ◽  
Neuronal Loss ◽  
Induced Pluripotent Stem Cell ◽  
Related Factor ◽  
Induced Pluripotent ◽  
Novel Therapeutic

Neurodegenerative disorders are caused by progressive neuronal loss, and there is no complete treatment available yet. Neuroinflammation is a common feature across neurodegenerative disorders and implicated in the progression of neurodegeneration. Dysregulated activation of microglia causes neuroinflammation and has been highlighted as a treatment target in therapeutic strategies. Here, we identified novel therapeutic candidate ALGERNON2 (altered generation of neurons 2) and demonstrate that ALGERNON2 suppressed the production of proinflammatory cytokines and rescued neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced Parkinson’s disease model. ALGERNON2 stabilized cyclinD1/p21 complex, leading to up-regulation of nuclear factor erythroid 2–related factor 2 (Nrf2), which contributes to antioxidative and anti-inflammatory responses. Notably, ALGERNON2 enhanced neuronal survival in other neuroinflammatory conditions such as the transplantation of induced pluripotent stem cell–derived dopaminergic neurons into murine brains. In conclusion, we present that the microglial potentiation of the p21-Nrf2 pathway can contribute to neuronal survival and provide novel therapeutic potential for neuroinflammation-triggered neurodegeneration.

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