Neutrophils augment LPS-mediated pro-inflammatory signaling in human lung epithelial cells

Boots, Agnes W.; Gerloff, Kirsten; Bartholomé, Roger; Berlo, Damiën van; Ledermann, Kirstin; Haenen, Guido R.M.M.; Bast, Aalt; Schooten, Frederik‐Jan van; Albrecht, Catrin; Schins, Roel P. F.

doi:10.1016/j.bbamcr.2012.04.012

Cited by 39 publications

(44 citation statements)

References 59 publications

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“…Second, we did not use primary alveolar epithelial cells; however, there is a plethora of published studies validating the use of human BEAS-2B and A549 cells as an acceptable model of epithelial cell injury and for studying the LPS-induced effects in the airway epithelium. [11][12][13][14][15][16]25,[28][29][30][31][32][33][34][35] Third, further studies are needed to elucidate whether there are other mechanisms by which the pyrrol compound DTA0118 elicits its anti-inflammatory and antiapoptotic activities. Fourth, TLR4, Ikβα, and β-actin were not adjusted for the cell number.…”

Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

“…We chose A549 and BEAS-2B cell lines as representative human alveolar and bronchial epithelial cells because they have been implicated in the pathogenesis of sepsis-induced ARDS. [11][12][13][14][15][16] One of the most important determinants of lung severity is the magnitude of injury to the epithelial barrier. 2 Epithelial cells generate cytokines, chemokines, and antimicrobial peptides in response to inflammatory stimuli, 25,26 and airway epithelium controls lung inflammation and injury through NF-κB.…”

Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

“…2 Epithelial cells generate cytokines, chemokines, and antimicrobial peptides in response to inflammatory stimuli, 25,26 and airway epithelium controls lung inflammation and injury through NF-κB. 27 Numerous experimental studies have used human A549 alveolar and BEAS-2B bronchial epithelial cell lines to examine the acute lung inflammatory response induced by LPS, as an acceptable, validated, and suitable in vitro airway epithelial injury model based on the initial steps of the development of sepsis and ARDS [11][12][13][14][15][16]25,[28][29][30] and continue being extensively used. [31][32][33][34][35] We selected E. coli LPS because it has been used in most endotoxin-induced lung injury models 36,37 and LPS is a key pathogen recognition molecule for sepsis 27 that induces apoptosis in lung cells.…”

Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

“…Based on a well-established protocol of the National Cancer Institute of the United States, 9 we used a validated screening strategy to identify potential therapeutic molecules by examining the effects of a novel family of tri-and tetrasubstituted pyrrols, which were previously studied by our group. 10 In the present study, we report the marked anti-inflammatory and antiapoptotic properties of a compound termed by us as DTA0118 in a well-established in vitro LPSinduced airway epithelial cell injury model, [11][12][13][14][15][16] based on the initial steps of the development of sepsis and sepsis-induced ARDS, using human alveolar A549 and human bronchial BEAS-2B cells. We used rhein and emodin, two anthracenederived anthraquinones with proven activity against the effects of LPS, 17 as reference compounds.…”

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confidence: 99%

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Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates

Cabrera-Benítez

Pérez-Roth

Ramos-Nuez

et al. 2016

Laboratory Investigation

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Inflammation and apoptosis are crucial mechanisms for the development of the acute respiratory distress syndrome (ARDS). Currently, there is no specific pharmacological therapy for ARDS. We have evaluated the ability of a new family of 1,2,3,5-tetrasubstituted pyrrol compounds for attenuating lipopolysaccharide (LPS)-induced inflammation and apoptosis in an in vitro LPS-induced airway epithelial cell injury model based on the first steps of the development of sepsis-induced ARDS. Human alveolar A549 and human bronchial BEAS-2B cells were exposed to LPS, either alone or in combination with the pyrrol derivatives. Rhein and emodin, two representative compounds with proven activity against the effects of LPS, were used as reference compounds. The pyrrol compound that was termed DTA0118 had the strongest inhibitory activity and was selected as the lead compound to further explore its properties. Exposure to LPS caused an intense inflammatory response and apoptosis in both A549 and BEAS-2B cells. DTA0118 treatment downregulated Toll-like receptor-4 expression and upregulated nuclear factor-κB inhibitor-α expression in cells exposed to LPS. These anti-inflammatory effects were accompanied by a significantly lower secretion of interleukin-6 (IL-6), IL-8, and IL-1β. The observed antiapoptotic effect of DTA0118 was associated with the upregulation of antiapoptotic Bcl-2 and downregulation of proapoptotic Bax and active caspase-3 protein levels. Our findings demonstrate the potent anti-inflammatory and antiapoptotic properties of the pyrrol DTA0118 compound and suggest that it could be considered as a potential drug therapy for the acute phase of sepsis and septic ARDS. Further investigations are needed to examine and validate these mechanisms and effects in a clinically relevant animal model of sepsis and sepsis-induced ARDS.

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Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

Section: Inhibition Of Lps-induced Airway Cell Injury Ne Cabrera-benímentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates

Cabrera-Benítez

Pérez-Roth

Ramos-Nuez

et al. 2016

Laboratory Investigation

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“…Recent studies have reported that LPS enables the production of ROS, leading to lipid peroxidation in lungs and resulting in lung damage (39)(40)(41). Therefore we measured the antioxidant GSH levels and catalase enzyme activities, as well as lipid peroxidation levels that may reflect intracellular defenses.…”

Section: Discussionmentioning

confidence: 99%

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

Vicil¹,

Erdoğan²

2015

Turk J Med Sci

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Background/aim: Human alveolar epithelial cells play a critical role in the pathogenesis of lung diseases. The objective of this study is to determine the contribution of beraprost sodium, a prostaglandin I 2 (PGI 2 ) analogue, to inflammatory and oxidative events in response to lipopolysaccharide (LPS) in airway epithelial cells.Materials and methods: Human pulmonary alveolar epithelial cells (A549) were pretreated with 10 µM beraprost sodium 30 min before stimulation with 1 µg/mL LPS for 24 h. The cellular viability assessments were evaluated by quantitative MTT test. Catalase activity and glutathione and lipid peroxidation levels were determined using spectrophotometric techniques. mRNA expression analyses were performed by real-time qRT-PCR. Results:The endotoxin induced a dose-dependent increase in proliferation of the cells, which was suppressed by the beraprost sodium treatment. LPS increased the expressions of TNF-α and IL-1β genes by 8-and 2.5-fold, respectively. It also induced lipid peroxidation and depleted cellular antioxidant capacity. Pretreatments of the cells with beraprost sodium significantly reversed the inflammation and suppressed oxidative stress. Conclusion:These findings suggest that beraprost sodium will provide a pivotal molecular basis for the design of new therapeutic strategies to cure endotoxin-induced lung injury, although additional comprehensive studies are still required.

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BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses

et al. 2015

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Control of histone acetylation is a part of the epigenetic mechanism that regulates gene expression and chromatin architecture. The members of the bromodomain and extra terminal domain (BET) protein family are a group of epigenetic readers that recognize histone acetylation, whereas histone deacetyl- ases such as sirtuin 1 (SIRT1) function as epigenetic erasers. We observed that BET inhibition by the specific inhibitor JQ1 upregulated SIRT1 expression and activated SIRT1. Moreover, we observed that BET inhibition functionally reversed the pro-inflammatory effect of SIRT1 inhibition in a cellular lung disease model. SIRT1 activation is desirable in many age-related, metabolic and inflammatory diseases; our results suggest that BET protein inhibition would be beneficial in treatment of those conditions. Most importantly, our findings demonstrate a novel mechanism of SIRT1 activation by inhibition of the BET proteins.

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Neutrophils augment LPS-mediated pro-inflammatory signaling in human lung epithelial cells

Cited by 39 publications

References 59 publications

Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates

Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses

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