Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Suzuki, Tomoko; Yamashita, Cory; Zemans, Rachel L.; Briones, Natalie; Linden, Annemie Van der; Downey, Gregory P.

doi:10.1165/rcmb.2008-0157oc

Cited by 63 publications

(50 citation statements)

References 78 publications

(97 reference statements)

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“…Various substances such as quercetin, 3-nitrobenzanthrone, arsenic, and marijuana smoke condensate trigger p53-dependent apoptosis in BEAS-2B cells, which is partially suppressed Kim et al, 2013). In particular, both pharmacologic inhibition and siRNA-mediated gene silencing of -tosis in BEAS-2B cells (Suzuki et al, 2009). Our results -fore, we suppose that Ag-NPs triggered p53-dependent apoptosis in BEAS-2B cells.…”

Section: It Is Critical To Assess Potential Impacts Of Nps Onsupporting

confidence: 48%

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

et al. 2014

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-Deregulated apoptosis has been associated with many lung diseases. Although many studies have reported the apoptotic effects exhibited by silver nanoparticles (Ag-NPs) in various circumstances, the apoptosis mechanism of Ag-NPs is unclear. We investigated oxidative stress and apoptosis in human normal bronchial epithelial (BEAS-2B) cells to elucidate the role of p53 in apoptosis by Ag-NPs. First, dispersion and stability of Ag-NPs improved using bronchial epithelial cell growth medium with 5% fetal bovine serum. Then, we observed oxidative stress in BEAS-2B cells exposed to Ag-NPs. Second, we carried out a cell death assay to measure DNA fragmentation as a biomarker of apoptosis. BEAS--mentation. We also found that apoptosis-related genes (caspase-3, Bax, and Bcl-2) were regulated by AgNPs, which was detected by mRNA and protein levels. These results suggest that Ag-NPs induced p53-Ag-NPs in pulmonary disease. Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.39, No.3, 401-412, 2014 Vol. 39 No. 3 401 lar and DNA damage (Risom et al., 2005). DNA damage induces extracellular and intracellular signals that trigger the onset of a signaling cascade with characteristic biochemical and morphological features, including nuclear condensation, membrane blebbing, and DNA fragmentation, leading ultimately to cell death (Johnson et al., 1996). This is called apoptosis, which is essential for the normal functioning and survival of multi-cellular organisms. However, deregulated apoptosis has been associated with many lung diseases because toxic contents are released from apoptotic cells unless the cells are quickly recognized or ingested by phagocytes (Pandya et al., 2006).The p53 gene regulates the apoptosis pathway (Korsmeyer, 1995;Yang and Duerksen-Hughes, 1998) and is tightly controlled through a complex series of events including translational regulation, interaction with regu--cations including multisite phosphorylation and acetylation (Giaccia and Kastan, 1998;Meek, 1999;Prives and Hall, 1999). In particular, phosphorylation of the serine-15 (Ser-15) residue due to DNA damage plays an important role in p53-mediated apoptosis (Dumaz and Meek, 1999;Siliciano et al., 1997;Unger et al., 1999). This activation of p53 leads to expression of its downstream effectors such as Bax, Bcl-2 and caspase-3, resulting in apoptosis (Martin and Elkon, 2004).In this study, we hypothesized that Ag-NPs induce apoptosis via the p53 signaling pathway in normal human lung bronchial epithelial (BEAS-2B) cells. Although many reports have shown apoptotic effects of Ag-NPs in various circumstances (Foldbjerg et al., 2009;Li et al., 2010;Miura and Shinohara, 2009;Piao et al., 2011), the were used to elucidate the role of p53 in apoptosis by Ag--sion of TiO 2 NPs improved by adding bovine serum albumin (BSA) or fetal bovine serum (FBS) to the medium (Ji et al., 2010). Thus, Ag-NPs were dispersed in bronchial epithelial growth medium (BEGM) with 5% FBS and were characterized. Then, we observed ROS generation...

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Section: It Is Critical To Assess Potential Impacts Of Nps Onsupporting

confidence: 48%

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

et al. 2014

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“…Consistent with this, we found lower elastase activity in BALF from mice treated with pioglitazone. Elastase aggravates ALI by increasing endothelial and epithelial permeability [32,33], proteolytic cleavage of surfactant proteins [34] and induction of apoptosis [35]. The in vivo importance of neutrophil elastase in ALI is further corroborated in studies using elastase-deficient mice [36] or employing specific inhibitors [37].…”

Section: Discussionmentioning

confidence: 94%

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

2012

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Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Activation and recruitment of neutrophils are regarded as key mechanisms in the progression of ALI. As pioglitazone holds potent pleiotropic anti-inflammatory effects, we explored its effects during ALI.C57Bl/6 mice were exposed to aerosolised lipopolysaccharides (LPSs) (500 mg?mL) and their alveolar, interstitial and intravascular neutrophils were assessed 4 h later. Lung permeability changes were evaluated by fluorescein isothiocyanate-dextran clearance and protein content in the bronchoalveolar lavage fluid. In vitro, human isolated neutrophils were pretreated with piolitazone (10 mM, for 1 or 3 h) and then activated with N-formyl-L-methionyl-L-leucyl-Lphenylalanine. Neutrophil activation, adhesion, release and formation of reactive oxygen species (ROS) and phagocytosis were measured thereafter.Pioglitazone treatment before or after induction of ALI significantly diminished alveolar (reduction by 73% and 67%, respectively) and interstitial neutrophil influx (reduction by 55% and 63%, respectively) and reduced lung permeability changes (reduction by 64% and 58%, respectively) indicating a protective role of pioglitazone treatment in ALI. Moreover, pioglitazone significantly reduced degranulation and adhesion of neutrophils without affecting ROS formation and release or bacterial phagocytosis.Pioglitazone reduces recruitment and activation of neutrophils thereby preventing LPS-induced ALI. Our results imply a potential role for pioglitazone treatment in the management of ALI.

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“…Similarly, release of elastase from migrating neutrophils has been shown to cleave E-cadherin, resulting in b-cateninedependent signaling events and subsequent proliferative signals. 116 Thus, an emerging paradigm has evolved that links inflammation-induced changes in epithelial intercellular junctions to profound effects on natural functions of the epithelium.…”

Section: Neutrophil-epithelial Interactionsmentioning

confidence: 99%

Neutrophil-Epithelial Interactions

Parkos

2016

The American Journal of Pathology

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Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Cited by 63 publications

References 78 publications

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

Neutrophil-Epithelial Interactions

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