The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter

Hirota, Jeremy A.; Hirota, Simon A.; Warner, Stephanie; Stefanowicz, Dorota; Shaheen, Furquan; Beck, Paul L.; MacDonald, Justin A.; Hackett, Tillie-Louise; Sin, Don D.; Eeden, Stephan Van; Knight, Darryl A.

doi:10.1016/j.jaci.2011.11.033

Cited by 150 publications

(170 citation statements)

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“…Our understanding of the role of inflammasome activation in human asthma is limited by the small number of studies using clinical samples. A recent study has shown that the NLPR3 inflammasome mediated the neutrophilic airway inflammation induced by particles with a 50% cut-off aerodynamic diameter of 10 mm [15], demonstrating that nonmicrobial triggers can influence the accumulation of neutrophils in the airway. Infections such as Chlamydophila pneumoniae and respiratory syncytial virus (which also result in neutrophilic bronchitis) induce NLRP3 inflammasomemediated IL-1b release [23,24].…”

Section: Discussionmentioning

confidence: 99%

“…The NLRP3 inflammasome is the most extensively characterised, and emerging data in humans and mice suggest that caspase-4/5 and caspase-11, respectively, contribute to NLRP3 inflammasome activation [12][13][14]. In human airways, a functional NLRP3 inflammasome has been identified in airway epithelial cells [15], and peripheral blood neutrophils express all components of the NLRP3 inflammasome, as well as IL-1b [16]; however, there is little data reporting the expression of NLRP3 inflammasome components in other cells from the airways in patients with asthma. A number of bacterial pathogens have been shown to require both TLR2 and inflammasome signalling to elicit the host immune response [17][18][19] and, while we have previously investigated the expression of TLR2 in asthma subtypes, the expression of inflammasome-associated proteins and IL-1b in asthma subtypes is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Elevated expression of the NLRP3 inflammasome in neutrophilic asthma

Simpson

Phipps

Baines

et al. 2013

European Respiratory Journal

226

191

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Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1b is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1b requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1b endotype associated with the nucleotide-binding domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic subtype of asthma.Participants with asthma (n585) and healthy controls (n527) underwent clinical assessment, spirometry and sputum induction. Sputum was processed for differential cell count, gene expression and protein mediators. NLRP3 and caspase-1 expression was also determined by immunocytochemistry. Sputum macrophages were isolated (n58) and gene expression of NLRP3 and IL-1b determined.There was significantly elevated gene expression of NLRP3, caspase-1, caspase-4, caspase-5 and IL-1b in participants with neutrophilic asthma. Protein levels of IL-1b were significantly higher in those with neutrophilic asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein.NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the inflammation process observed in this asthma phenotype through production of IL-1b. @ERSpublications The NLRP3 inflammasome may be a key regulator of neutrophilic airway inflammation in asthma through production of IL-1b

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated expression of the NLRP3 inflammasome in neutrophilic asthma

Simpson

Phipps

Baines

et al. 2013

European Respiratory Journal

226

191

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“…Alveolar macrophages are the primary innate immune phagocytic cells at the air tissue interface responsible for clearance of particulate matters [13,14]. Inflammasome, an oligomer of intracellular proteins, is now believed to be the link between innate immune response to dust and lung inflammation; inorganic particulate matters including silica have been reported to trigger inflammasome activation with resultant cytokine production in alveolar macrophages [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): Effects of lowered serum zinc level on the toxicity

Shimada

Miyake

Kenmotsu

et al. 2015

Folia Histochem Cytobiol.

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Introduction. We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. Material and methods. Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1b as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. Results. Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1b, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1b-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. Conclusions. These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD.

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“…Inhaled air pollution can deposit directly into the lungs or be swept up the mucociliary ladder to be ingested into the gastrointestinal tract. In the lung, particulate air pollution can promote inflammatory cell recruitment [6], while in the gut it can exacerbate intestinal inflammation in experimental models of IBD and induce changes in the intestinal microbiome [7]. The mechanisms responsible for these observations may converge on common innate immune pathways at these mucosal sites [8].…”

mentioning

confidence: 99%

“…The mechanisms responsible for these observations may converge on common innate immune pathways at these mucosal sites [8]. In a mouse model of air pollution exposure to the lungs, we have previously demonstrated the involvement of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in the initiation of an innate immune response in the airways [6], while in the gut, we have shown that the NLRP3 inflammasome is a key player in innate immunity and helps to maintain intestinal mucosal homeostasis through regulation of the intestinal microbiome [9]. Understanding how air pollution exposure modulates innate immune signalling in these two organs may yield new insight into the pathogenesis of both airway diseases and IBD.…”

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confidence: 99%

Airway diseases and inflammatory bowel diseases: is it something in the air (pollution)?

et al. 2015

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Our group has recently discussed the exciting European Respiratory Journal publication by BRASSARD et al.[1] that shows an increased incidence of the inflammatory bowel diseases (IBD) in subjects with airway disease. In this population-based cohort study, the incidence of Crohn's disease was higher in the asthma (by 27%) and chronic obstructive pulmonary disease (COPD) (by 55%) groups relative to the general population. This study complements other recent observations showing increased gut permeability in those with COPD relative to healthy controls [2], which is a potential mechanism for development of IBD. Taken together, these data suggest a common link in the pathogenesis of IBD and airway disease; however, the mechanisms responsible for these interesting observations remain unclear.

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The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter

Cited by 150 publications

References 58 publications

Elevated expression of the NLRP3 inflammasome in neutrophilic asthma

Elevated expression of the NLRP3 inflammasome in neutrophilic asthma

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): Effects of lowered serum zinc level on the toxicity

Airway diseases and inflammatory bowel diseases: is it something in the air (pollution)?

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