Inhaled silica nanoparticles exacerbate atherosclerosis through skewing macrophage polarization towards M1 phenotype

Stachyra, Kamila; Wiśniewska, Anna; Kuś, Katarzyna; Rolski, Filip; Czepiel, Klaudia; Chmura, Łukasz; Majka, Grzegorz; Surmiak, Marcin; Polaczek, Justyna; Eldik, Rudi van; Suski, Maciej; Olszanecki, Rafał

doi:10.1016/j.ecoenv.2021.113112

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…More studies are necessary to confirm the preliminary results which point to complex samples-PM, PMΔC-seemingly affecting the autoimmune process and IL-6-PAD4 axis at the same time, whereas nano-oxide suspensions-SiNPs, FeNPs-induce massive upregulation of TNFα implicating the M1 polarization as a potential pathway for aggravation of joint inflammation. The effect of the latter has recently been confirmed in arthritis model including inhalation with the very same suspensions of nano-oxides (Stachyra et al 2022). Our previous study confirms these data.…”

Section: Discussionsupporting

confidence: 86%

“…The incidence of autoimmune diseases was found to be higher in urban areas (Chiang et al 2016;Gan et al 2013;Hart et al 2009Hart et al , 2013. Moreover, it has been proven recently that several factors present in the air pollution particulate matter promote the development of atherosclerosis and impact the macrophage polarization towards M1 inflammatory phenotype (Stachyra et al 2022). Therefore, it is plausible that other autoimmune processes could also be affected by inhalation of certain components of the particulate matter which would provide the explanation for the association between urbanization and incidence/exacerbation of RA.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, mice inhaled with the same PM samples (crude PM, organic-devoid PM, silica and ferric nanoparticles) for up to 16 weeks, in the model of experimental autoimmune encephalomyelitis (manuscript in preparation) as well as in the atherosclerosis model (Stachyra et al 2022) did not develop any symptoms of joint inflammation. It indicates that PM inhalation alone is not able to induce joint inflammation but CII immunization is required.…”

Section: Clinical Symptomsmentioning

confidence: 99%

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The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

Nowak

Majka

Śróttek

et al. 2022

Arch. Immunol. Ther. Exp.

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Air pollution is considered to be one of a risk factor for rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is commonly used as a mouse model of human RA. However, the impact of specific particulate matter (PM) components on the incidence and severity of RA has still not been established. The aim of this study was to develop an experimental model of CIA suitable to test arthritogenicity of inhaled PM. A mild form of CIA was induced in DBA1/J mice inhaled with various components of SRM 1648a PM. The incidence and severity of arthritis was assessed, and the selected serum markers of autoimmunity and inflammation were determined. Clinical arthritis was observed from the booster CII immunisation onward. Anti-cyclic citrullinated peptide antibodies, a diagnostic marker of RA, were detected in serum of these mice. All inhaled pollutants, crude PM, PM with reduced organic content, ferric, and silica nanoparticles markedly increased CIA incidence and severity. The fastest progression of CIA development was caused by crude PM and was linked to enhanced serum levels of anti-CII IgG, the prominent arthritogenic autoantibodies. On the other hand, inhaled nanoparticles enhanced serum levels of TNFα, a major proinflammatory arthritogenic cytokine. We recommend this experimental model of mild CIA to test the mechanisms of arthritis exacerbation by inhaled air pollutants. Further studies are necessary to determine whether PM-aggravated arthritis is caused by inflammatory mediators translocated from inflamed lung into systemic circulation or whether PM translocated into the bloodstream directly exacerbate joint inflammation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Clinical Symptomsmentioning

confidence: 99%

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The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

Nowak

Majka

Śróttek

et al. 2022

Arch. Immunol. Ther. Exp.

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“…Usually, SiNPs are recognized as PAMPs that induce transduction of intracellular signals, among which NF‐κB dominants the transcription of most effector molecules. Previous studies have shown that the upregulation or enhancement of nuclei transmission of NF‐κB promotes LPS‐induced acute kidney injury, atherosclerosis, and liver cirrhosis 25–27 . Here, we find upregulation of NF‐κB as evidence of its regulation on SiNPs‐induced macrophage inflammatory response.…”

Section: Discussionsupporting

confidence: 68%

“…Previous studies have shown that the upregulation or enhancement of nuclei transmission of NF-κB promotes LPS-induced acute kidney injury, atherosclerosis, and liver cirrhosis. [25][26][27] Here, we find upregulation of NF-κB as evidence of its regulation on SiNPs-induced macrophage inflammatory response.…”

Section: Discussionmentioning

confidence: 51%

NF‐κB mediates silica‐induced pulmonary inflammation by promoting the release of IL‐1β in macrophages

Zhang

Yang

et al. 2022

Environmental Toxicology

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Long‐term exposure to respirable silica particles causes pulmonary inflammation and fibrosis primarily promoted by cytokines released from alveolar macrophages, yet the underlying mechanism is still unclear. From the perspective of nuclear factor kappa B (NF‐κB), we studied the mechanism of IL‐1β biosynthesis and release. Utilizing BAY 11‐7082, an NF‐κB specific inhibitor, we showed the alteration of macrophage viability and examined the expression of both IL‐1β and NF‐κB in vitro. We found that silica nanoparticles (SiNPs) were internalized by macrophages and caused damage to cell integrity. The immunofluorescence assay showed that SiNPs exposure enhanced the expression of IL‐1β and NF‐κB, which could be effectively suppressed by BAY 11‐7082. Besides, we built silica exposure mouse model by intratracheally instilling 5 mg of SiNPs and checked the effect of silica exposure on pulmonary pathological changes. Consistently, we found an upregulation of IL‐1β and NF‐κB after SiNPs exposure, along with the aggravated inflammatory cell infiltration, thickened alveolar wall, and enhanced expression of collagens. In conclusion, SiNPs exposure causes pulmonary inflammation and fibrosis that is regulated by NK‐κB through upregulating IL‐1β in alveolar macrophages.

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Changes in the liver proteome in apoE knockout mice exposed to inhalation of silica nanoparticles indicate mitochondrial damage and impairment of ER stress responses associated with microvesicular steatosis

Stachyra

Suski

Ulatowska-Białas

et al. 2022

Environ Sci Pollut Res

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The adverse effects of air pollution on the cardiovascular system have been well documented. Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular events. However, the influence of exposure to airborne particles on the development of NAFLD is less recognised. The aim of this study was to investigate the impact of silica nanoparticles (SiNPs) on the development of liver steatosis. We used molecular and proteomic SWATH-MS methods to investigate the changes in the liver proteome of apolipoprotein E-knockout mice (apoE−/− mice) exposed to SiNPs for 4 months in a whole-body exposure chamber. Exposure to SiNPs evoked microvesicular liver steatosis in apoE−/− mice. Quantitative liver proteomics showed significant downregulation of ribosomal proteins and endoplasmic reticulum proteins. Gene expression analysis revealed a reduced level of proteins related to endoplasmic reticulum stress. Treatment with SiNPs decreased mitochondrial membrane potential and increased the production of reactive oxygen species in cultured HepG2 cells. This is the first report that inhalation exposure to SiNPs induces microvesicular steatosis and significant changes in the liver proteome in vivo. Our results highlight the important role of silica and point to the ER stress response and mitochondrial dysfunction as potential mechanisms responsible for the increase in fatty liver by SiNPs.

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Inhaled silica nanoparticles exacerbate atherosclerosis through skewing macrophage polarization towards M1 phenotype

Cited by 12 publications

References 43 publications

The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

NF‐κB mediates silica‐induced pulmonary inflammation by promoting the release of IL‐1β in macrophages

Changes in the liver proteome in apoE knockout mice exposed to inhalation of silica nanoparticles indicate mitochondrial damage and impairment of ER stress responses associated with microvesicular steatosis

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