Abstract:
BACKGROUND:The alveolar macrophage (AM) - first line of innate immune defence against pathogens and environmental irritants - constitutively expresses peroxisome-proliferator activated receptor γ (PPARγ). PPARγ ligand-induced activation keeps the AM quiescent, and thereby contributes to combat invaders and resolve inflammation by augmenting the phagocytosis of apoptotic neutrophils and inhibiting an excessive expression of inflammatory genes. Because of these presumed anti-inflammatory functions of PPARγ we tested the hypothesis, whether reduced functional receptor availability in mutant mice resulted in increased cellular and molecular inflammatory response during acute inflammation and/or in an impairment of its resolution. METHODS:To address this hypothesis we examined the effects of a carbon-nanoparticle (CNP) lung challenge, as surrogate for non-infectious environmental irritants, in a murine model carrying a dominant-negative point mutation in the ligand-binding domain of PPARγ (P465L/wt). Animals were instilled intratracheally with Printex 90 CNPs and bronchoalveolar lavage (BAL) was gained 24 h or 72 h after instillation to investigate its cellular and protein composition. RESULTS:Higher BAL cell numbers - due to higher macrophage counts - were found in mutants irrespective of treatment. Neutrophil numbers in contrast were slightly lower in mutants. Intratracheal CNP instillation resulted in a profound recruitment of inflammatory neutrophils into the alveolus, but genotype related differences at acute inflammation (24 h) and resolution (72 h) were not observed. There were no signs for increased alveolar-capillary membrane damage or necrotic cell death in mutants as determined by BAL protein and lactate-dehydrogenase content. Pro-inflammatory macrophage-derived cytokine osteopontin was higher, but galectin-3 lower in female mutants. CXCL5 and lipocalin-2 markers, attributed to epithelial cell stimulation did not differ. CONCLUSIONS:Despite general genotype-related differences, we had to reject our hypothesis of an increased CNP induced lung inflammation and an impairment of its resolution in PPARγ defective mice. Although earlier studies showed ligand-induced activation of nuclear receptor PPARγ to promote resolution of lung inflammation, its reduced activity did not provide signs of resolution impairment in the settings investigated here.
journal_name
Part Fibre Toxicoljournal_title
Particle and fibre toxicologyauthors
Götz AA,Vidal-Puig A,Rödel HG,de Angelis MH,Stoeger Tdoi
10.1186/1743-8977-8-28subject
Has Abstractpub_date
2011-09-20 00:00:00pages
28issn
1743-8977pii
1743-8977-8-28journal_volume
8pub_type
杂志文章abstract:BACKGROUND:The exact role of primary nanoparticle (NP) size and their degree of agglomeration in aerosols on the determination of pulmonary effects is still poorly understood. Smaller NP are thought to have greater biological reactivity, but their level of agglomeration in an aerosol may also have an impact on pulmonar...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-10-48
更新日期:2013-10-04 00:00:00
abstract:BACKGROUND:There is a great need for screening tools capable of rapidly assessing nanomaterial toxicity. One impediment to the development of reliable in vitro screening methods is the need for accurate measures of cellular dose. We present here a methodology that enables accurate determination of delivered to cell dos...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-11-20
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:In myeloid cells the inflammasome plays a crucial role in innate immune defenses against pathogen- and danger-associated patterns such as crystalline silica. Respirable mineral particles impinge upon the lung epithelium causing irreversible damage, sustained inflammation and silicosis. In this study we inves...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-10-3
更新日期:2013-02-12 00:00:00
abstract:BACKGROUND:Combustion generated particulate matter is deposited in the respiratory tract and pose a hazard to the lungs through their potential to cause oxidative stress and inflammation. We have previously shown that combustion of fuels and chlorinated hydrocarbons produce semiquinone-type radicals that are stabilized...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-6-11
更新日期:2009-04-17 00:00:00
abstract:BACKGROUND:Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO ...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-9-22
更新日期:2012-06-19 00:00:00
abstract:BACKGROUND:Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled p...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-8-19
更新日期:2011-06-09 00:00:00
abstract:BACKGROUND:Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-11-3
更新日期:2014-01-09 00:00:00
abstract:BACKGROUND:Given the tremendous potential for graphene quantum dots (QDs) in biomedical applications, a thorough understanding of the interaction of these materials with macrophages is essential because macrophages are one of the most important barriers against exogenous particles. Although the cytotoxicity and cellula...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-018-0279-8
更新日期:2018-11-13 00:00:00
abstract:INTRODUCTION:Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on a...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-6-7
更新日期:2009-03-13 00:00:00
abstract:BACKGROUND:Carbon nanotubes (CNT) can interact with the biological environment, which could participate in their associated toxicity. We recently demonstrated that pH is an important player of CNT fate inside macrophages. We wanted to further characterize such process, and therefore designed a study dedicated to deciph...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-016-0175-z
更新日期:2016-11-24 00:00:00
abstract:BACKGROUND:Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the d...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-017-0212-6
更新日期:2017-08-22 00:00:00
abstract:BACKGROUND:Mitochondria are both a sensitive target and a primary source of oxidative stress, a key pathway of air particulate matter (PM)-associated diseases. Mitochondrial DNA copy number (MtDNAcn) is a marker of mitochondrial damage and malfunctioning. We evaluated whether ambient PM exposure affects MtDNAcn in a hi...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-10-17
更新日期:2013-04-29 00:00:00
abstract:BACKGROUND:Nanometer silicon dioxide (nano-SiO2) has a wide variety of applications in material sciences, engineering and medicine; however, the potential cell biological and proteomic effects of nano-SiO2 exposure and the toxic mechanisms remain far from clear. RESULTS:Here, we evaluated the effects of amorphous nano...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-7-1
更新日期:2010-01-19 00:00:00
abstract:BACKGROUND:Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement ...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-7-25
更新日期:2010-09-11 00:00:00
abstract:BACKGROUND:Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer sim...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-020-00392-w
更新日期:2020-12-07 00:00:00
abstract::This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP) following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-2-10
更新日期:2005-10-21 00:00:00
abstract::In their Commentary Saber et al. (Part Fibre Toxicol 16: 44, 2019) argue that chronic inhalation studies in rats can be used for assessing the lung cancer risk of insoluble nanomaterials. The authors make several significant errors in their interpretation and representation of the underlying science. In this Letter to...
journal_title:Particle and fibre toxicology
pub_type: 评论,信件
doi:10.1186/s12989-020-00365-z
更新日期:2020-07-16 00:00:00
abstract:BACKGROUND:Carbon load in airway macrophages (AM) has been proposed as an internal marker to assess long-term exposure to combustion-derived pollutant particles. However, it is not known how this biomarker is affected by changes in exposure. We studied the clearance kinetics of black carbon (BC) in AM, obtained by sput...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-018-0250-8
更新日期:2018-03-14 00:00:00
abstract:BACKGROUND:Even though a continuously high number of in vitro studies on nanoparticles are being published, the issue of correct dose matter is often not sufficiently taken into account. Due to their size, the diffusion of nanoparticles is slower, as compared to soluble chemicals, and they sediment slowly. Therefore, t...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-018-0278-9
更新日期:2018-10-30 00:00:00
abstract::Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on t...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章,评审
doi:10.1186/1743-8977-10-15
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND:Air pollution is a recognized aggravating factor for pulmonary diseases and has notably deleterious effects on asthma, bronchitis and pneumonia. Recent studies suggest that air pollution may also cause adverse effects in the gastrointestinal tract. Accumulating experimental evidence shows that immune respons...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-017-0227-z
更新日期:2017-11-22 00:00:00
abstract:BACKGROUND:Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may p...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-016-0143-7
更新日期:2016-06-10 00:00:00
abstract::There are certain concerns regarding the safety for the environment and human health from the use of engineered nanoparticles (ENPs) which leads to unintended exposures, as opposed to the use of ENPs for medical purposes. This review focuses on the unintended human exposure of ENPs. In particular, possible effects in ...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章,评审
doi:10.1186/1743-8977-7-42
更新日期:2010-12-21 00:00:00
abstract::The uncertainty regarding the effects and risks of nanomaterials on human health and the environment, and how they should be tested and assessed in the context of current regulations, is clearly holding back the full exploitation of the innovative potential of nanomaterials. To reduce this uncertainty, the European Un...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-017-0235-z
更新日期:2017-12-19 00:00:00
abstract:BACKGROUND:Using engineered nanomaterial-based toners, laser printers generate aerosols with alarming levels of nanoparticles that bear high bioactivity and potential health risks. Yet, the cardiac impacts of printer-emitted particles (PEPs) are unknown. Inhalation of particulate matter (PM) promotes cardiovascular mor...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/s12989-019-0335-z
更新日期:2020-01-29 00:00:00
abstract:BACKGROUND:Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the...
journal_title:Particle and fibre toxicology
pub_type: 信件
doi:10.1186/s12989-019-0315-3
更新日期:2019-08-16 00:00:00
abstract:BACKGROUND:Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear. RESULTS:We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-10-39
更新日期:2013-08-13 00:00:00
abstract:: Air Pollution has been associated with significant adverse health effects leading to increased morbidity and mortality. Cumulative epidemiological and experimental data have shown that exposure to air pollutants lead to increased cardiovascular ischemic events and enhanced atherosclerosis. It appears that these assoc...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-6-24
更新日期:2009-09-18 00:00:00
abstract:BACKGROUND:It has been suggested that carbon nanotubes might conform to the fibre pathogenicity paradigm that explains the toxicities of asbestos and other fibres on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fibre paradigm but only ...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-8-15
更新日期:2011-05-13 00:00:00
abstract:UNLABELLED:A novel methodology to detect unlabeled inorganic nanoparticles was experimentally demonstrated using a mixture of nano-sized (70 nm) and submicron (250 nm) silicon dioxide particles added to mammalian tissue. The size and concentration of environmentally relevant inorganic particles in a tissue sample can b...
journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-5-18
更新日期:2008-12-03 00:00:00