Amorphous silica nanoparticles induce inflammation via activation of NLRP3 inflammasome and HMGB1/TLR4/MYD88/NF-kb signaling pathway in HUVEC cells

Liu, Xuting; Lü, Bin; Fu, Juanli; Zhu, Xiaolin; Song, Erqun; Song, Yang

doi:10.1016/j.jhazmat.2020.124050

Cited by 73 publications

(65 citation statements)

References 57 publications

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“…Our results, therefore, suggest that NANPs delivered by cationic dendrimers are perceived by immune cells as danger signals, hence the induction of IL-1α, IL-6, and IL-8 [24]. Cationic nanoparticles activate the inflammasome, thereby contributing to the secretion of mature IL-1β, expression of which is induced by other stimuli [53][54][55]. The induction of IL-1β observed in supernatants from cells treated with NANP-dendrimer complexes is consistent with this knowledge; the data suggest that NANPs induce IL-1β expression whereas cationic dendrimers activate the inflammasome to produce mature IL-1β proteins.…”

Section: Discussionmentioning

confidence: 68%

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

et al. 2021

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Recent insights into the immunostimulatory properties of nucleic acid nanoparticles (NANPs) have demonstrated that variations in the shape, size, and composition lead to distinct patterns in their immunostimulatory properties. While most of these studies have used a single lipid-based carrier to allow for NANPs’ intracellular delivery, it is now apparent that the platform for delivery, which has historically been a hurdle for therapeutic nucleic acids, is an additional means to tailoring NANP immunorecognition. Here, the use of dendrimers for the delivery of NANPs is compared to the lipid-based platform and the differences in resulting cytokine induction are presented.

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Section: Discussionmentioning

confidence: 68%

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

et al. 2021

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“…ROS also promotes the transfer of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm (52). As DAMPs, HMGB1 can also activate NLRP3 through the TLR4-NF-kB pathways (53). After NLRP3 is activated, NLRP3 forms NLRP3 inflammasome together with ASC and pro-caspase-1 (54).…”

Section: Liver Fibrosismentioning

confidence: 99%

Inflammasomes and Fibrosis

et al. 2021

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Fibrosis is the final common pathway of inflammatory diseases in various organs. The inflammasomes play an important role in the progression of fibrosis as innate immune receptors. There are four main members of the inflammasomes, such as NOD-like receptor protein 1 (NLRP1), NOD-like receptor protein 3 (NLRP3), NOD-like receptor C4 (NLRC4), and absent in melanoma 2 (AIM2), among which NLRP3 inflammasome is the most studied. NLRP3 inflammasome is typically composed of NLRP3, ASC and pro-caspase-1. The activation of inflammasome involves both “classical” and “non-classical” pathways and the former pathway is better understood. The “classical” activation pathway of inflammasome is that the backbone protein is activated by endogenous/exogenous stimulation, leading to inflammasome assembly. After the formation of “classic” inflammasome, pro-caspase-1 could self-activate. Caspase-1 cleaves cytokine precursors into mature cytokines, which are secreted extracellularly. At present, the “non-classical” activation pathway of inflammasome has not formed a unified model for activation process. This article reviews the role of NLRP1, NLRP3, NLRC4, AIM2 inflammasome, Caspase-1, IL-1β, IL-18 and IL-33 in the fibrogenesis.

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“…HUVEC is relatively easy to operate, and developing EC from stem cells may require more professional skills (Song et al, Year 2014). By using HUVEC, spherical MSN has been shown to induce cytotoxicity, oxidative stress and apoptosis, leading to EC dysfunction (Guo et al, 2018, 2016; Liu et al, 2020 year). However, the effect of the physical and chemical properties of MSNs on EC toxicity has not been studied yet.…”

Section: Introductionmentioning

confidence: 99%

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Teng¹,

Yang²,

Wang³

et al. 2021

J of Applied Toxicology

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Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA‐15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA‐15 indicates that SBA‐15 has high biocompatibility. Fibrous SBA‐15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA‐15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA‐15 types significantly increased Kruppel‐like factor 2 (KLF2) protein, irregular SBA‐15 (1), non‐aggregated spherical SBA‐15 (2) and aggregation The spherical SBA‐15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA‐15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO‐eNOS pathway, but the irregular spherical SBA‐15 reduces the eNOS modifier KLF4. The rod‐shaped SBA‐15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.

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Amorphous silica nanoparticles induce inflammation via activation of NLRP3 inflammasome and HMGB1/TLR4/MYD88/NF-kb signaling pathway in HUVEC cells

Cited by 73 publications

References 57 publications

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

Inflammasomes and Fibrosis

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

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