Carbon nanotubes provoke inflammation by inducing the pro-inflammatory genes IL-1β and IL-6

Qu, Chen; Wang, Lixin; He, Jianxun; Tan, Jianhua; Liu, Wei; Zhang, Shuping; Zhang, Chang-wen; Wang, Zhe; Jiao, Shouhai; Liu, Sijin; Jiang, Guibin

doi:10.1016/j.gene.2011.11.046

Cited by 37 publications

(19 citation statements)

References 22 publications

(27 reference statements)

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“…IL-6 has been shown to contribute to cardiovascular dysfunction induced by acute lung injury [62]. MWCNTs and SWCNTs have been shown to provoke inflammation by induction of the pro-inflammatory genes IL-1β and IL-6 [63]. Although not statistically significant, we also found elevated levels of IL-6, IL-10, IL-12, IL-13, KC and MIP1-α with the COOH and the N-doped MWCNTs.…”

Section: Discussionmentioning

confidence: 99%

Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

et al. 2012

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BackgroundThe exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs). It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury).MethodsOropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg) suspended in 100 μL of a surfactant saline (SS) solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade), and functionalized forms that were modified either by acid treatment (carboxylated, COOH) or nitrogenation (N-doped) and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R) injury were assessed at 1, 7 and 28 days post-aspiration.ResultsPulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF) revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but not the C-grade as compared to SS.ConclusionOur results suggest that oropharyngeal aspiration of MWCNT promotes increased susceptibility of cardiac tissue to ischemia/reperfusion injury without a significant pulmonary inflammatory response. The cardiac injury effects were observed at low concentrations of MWCNTs and presence of MWCNTs may pose a significant risk to the cardiovascular system.

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Section: Discussionmentioning

confidence: 99%

Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

et al. 2012

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“…There have also been a number of recent reports seeking to elucidate the mechanism underlying the toxicity of the CNTs. Alterations in reactive oxygen species (Azad et al, 2012;Pacurari et al, 2012), cell permeability, changes in enzymatic activity (Hitoshi et al, 2012) and activation of immunological responses (Qu et al, 2012) have been reported. Recently, CNT exposure has also been linked with fibrogenic (He et al, 2011), cytotoxic (Cavallo et al, 2012), genotoxic (Lindberg et al, 2009) neurotoxic (Wei et al, 2011;Wu et al, 2005) and carcinogenic (Sargent et al, 2012) responses.…”

Section: In Vivo Carbon Nanotube Delivery By Inhalationmentioning

confidence: 99%

Raman spectroscopy analysis and mapping the biodistribution of inhaled carbon nanotubes in the lungs and blood of mice

Ingle

Dervishi

Biriş

et al. 2012

J of Applied Toxicology

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Because of their small size, robust structure, and unique characteristics, carbon nanotubes (CNTs) are increasingly used in a variety of biomedical applications, materials, and products. As their use increases, so does the likelihood of unintended release and human exposure. Therefore, it is important to establish their potential biodistribution and biopersistence to better understand the potential effects of their exposure to humans. This study examines distribution of CNTs in CD-1 mice following exposure by inhalation of single-walled carbon nanotubes (SWCNTs) and investigates the possibility that inhaled nanoparticles could enter the circulatory system via the lungs. Raman spectroscopy was used to detect the presence of CNTs in lung tissue and blood based on their unique spectroscopic signatures. These studies have important implications concerning the potential effects of exposure to SWCNTs and about their use as potential transport vehicles in nanomedicine.

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“…The mechanism of increased abdominal wall PMC fibrotic gene expression is unclear. However, we believe that the progressive increases in fibrotic gene expression in abdominal wall PMC observed in our study represent pre-fibrotic changes that herald the formation of discreet fibrotic lesions and adhesions in the abdominal cavity, presumably initiated by the NT-induced leukocytic accumulation [ 19 ] and release of inflammatory cytokines [ 28 , 34 ]. Indeed, evidence of a pre-fibrotic response in the abdominal wall PMC was apparent from elevations in Lox , Col1a1 and Col3a1 mRNA expression, with NT causing a progressive increase in abdominal wall Lox and Col1a1 over 7 days.…”

Section: Discussionmentioning

confidence: 99%

Targeting lysyl oxidase reduces peritoneal fibrosis

Harlow

Deemter

et al. 2017

PLoS ONE

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BackgroundAbdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions.MethodsFemale C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile–BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro.ResultsNT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro.ConclusionOur results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

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Carbon nanotubes provoke inflammation by inducing the pro-inflammatory genes IL-1β and IL-6

Cited by 37 publications

References 22 publications

Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

Raman spectroscopy analysis and mapping the biodistribution of inhaled carbon nanotubes in the lungs and blood of mice

Targeting lysyl oxidase reduces peritoneal fibrosis

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