Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells

Johansson, Anne; Palmblad, Jan

doi:10.1016/j.lfs.2009.03.012

Cited by 12 publications

(12 citation statements)

References 21 publications

(25 reference statements)

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“…Moreover, the anti-inflammatory potential of EtOH was mimicked by EtP in lung epithelial cells. Johansson and Palmblad have demonstrated this anti-inflammatory potential previously (48). However, no underlying mechanism was described previous to the present study, to the best of our knowledge.…”

Section: Discussionsupporting

confidence: 42%

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells

Relja

Omid

Wagner

et al. 2015

International Journal of Molecular Medicine

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Abstract. Increases in pro-inflammatory cytokine levels and tissue-infiltrating leukocytes have been closely linked to increased systemic and local inflammation, which result in organ injury. Previously, we demonstrated the beneficial and hepatoprotective anti-inflammatory effects of acute ethanol (EtOH) ingestion in an in vivo model of acute inflammation. Due to its undesirable side-effects, however, EtOH does not represent a therapeutic option for treatment of acute inflammation. Therefore, in this study, we compared the effects of acute EtOH exposure with ethyl pyruvate (EtP) as an alternative anti-inflammatory drug in an in vitro model of hepatic and pulmonary inflammation. Human hepatocellular carcinoma cells Huh7 and alveolar epithelial cells A549 were stimulated with either interleukin (IL) IL-1β (1 ng/ml, 24 h) or tumor necrosis factor (TNF) (10 ng/ml, 4 h), and then treated with EtP (2.5-10 mM), sodium pyruvate (NaP, 10 mM) or EtOH (85-170 mM) for 1 h. IL-6 or IL-8 release from Huh7 or A549 cells, respectively, was measured by an enzyme-linked immunosorbent assay. Neutrophil adhesion to cell monolayers and CD54 expression were also analyzed. Bcl-2 and Bax gene expression was determined by RT-qPCR, and western blot analysis was performed to determine the mechanisms involved. Treating A549 cells with either EtOH or EtP significantly reduced the IL-1β-or TNF-induced IL-8 release, whereas treating Huh7 cells did not significantly alter IL-6 release. Similarly, neutrophil adhesion to stimulated A549 cells was significantly reduced by EtOH or EtP, whereas for Huh7 cells the tendency for reduced neutrophil adhesion rates by EtOH or EtP was not significant. CD54 expression was noticeably reduced in A549 cells, but this was not the case in Huh7 cells after treatment. The Bax/ Bcl-2 ratio was dose-dependently decreased by EtOH and by high-dose EtP in A549 cells, indicating a reduction in apoptosis, whereas this effect was not observed in Huh7 cells. The underlying mechanisms involve reduced phosphorylation of Akt and nuclear factor-κB (NF-κB) p65. We noted that as with EtP, EtOH reduced the inflammatory response in lung epithelial cells under acute inflammatory conditions. However, due to the low impact which EtP and EtOH had on the hepatocellular cells, our data suggest that both substances exerted different effects depending on the cellular entity. The possible underlying mechanisms involved the downregulation of Akt and the transcription factor NF-κB, but further research on this subject is required.

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Section: Discussionsupporting

confidence: 42%

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells

Relja

Omid

Wagner

et al. 2015

International Journal of Molecular Medicine

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“…Recent studies showed that in macrophage (Han et al, 2005) and endothelial cell (Johansson and Palmblad, 2009), EP interacts with NF-κB by directly targeting p65 subunit. Consistently, our in vivo studies demonstrated that EP treatment inhibited H-I-induced p65 nuclear translocation and expression of several NF-κB-responsive genes (TNF-α, IL-1α, IL-1β, COX-2 and iNOS), suggesting the involvement of such NF-κB modulation in the anti-inflammatory effect of EP following H-I.…”

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms

Shen

Liu

et al. 2010

Neurobiology of Disease

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Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an antiinflammatory effect in microglia by inhibiting NF-κB activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury.

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“…IL-8 release following treatment with EtOH or EtP. It has been reported that a short duration of incubation with EtP reduces the release of IL-8 in stimulated human endothelial and epithelial cells (3,29). The present study assessed the effects of pre-and post-treatment with EtOH, EtP or NaP for 1, 24 and 72 h on the IL-6-induced secretory potential of A549 cells to produce IL-8.…”

Section: Il-8 Release From the A549 Cellsmentioning

confidence: 95%

“…The concentrations of EtOH, EtP, NaP and IL-6 used were based on previous studies and our previous study to improve comparison of data (3,8,(29)(30)(31)(32). EtOH was used at 85 and 170 mM (0.5-1 vol −1 %; 4-7.9 mg EtOH ml −1 ), as described previously (28)(29)(30). Similarly, the concentrations of EtP (2.5 and 10 mM) and NaP (10 mM) were selected, according to previous studies (18,31).…”

Section: Methodsmentioning

confidence: 99%

Pre- or post-treatment with ethanol and ethyl pyruvate results in distinct anti-inflammatory responses of human lung epithelial cells triggered by interleukin-6

Relja

Omid

Schaible

et al. 2015

Molecular Medicine Reports

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Increased local and systemic levels of interleukin (IL)-6 are associated with inflammatory processes, including neutrophil infiltration of the alveolar space, resulting in lung injury. Our previous study demonstrated the beneficial anti-inflammatory effects of acute exposure to ethanol (EtOH) in an acute in vivo model of inflammation. However, due to its side-effects, EtOH is not used clinically. In the present study, the effects of EtOH and ethyl pyruvate (EtP) as an alternative anti-inflammatory drug prior to and following application of an IL-6 stimulus on cultured A549 lung epithelial cells were compared, and it was hypothesized that treatment with EtOH and EtP reduces the inflammatory potential of the A549 cells. Time- and dose-dependent release of IL-8 from the A549 cells was observed following stimulation with IL-6. The release of IL-8 from the A549 cells was assessed following treatment with EtP (2.5-10 mM), sodium pyruvate (NaP; 10 mM) or EtOH (85-170 mM) for 1, 24 or 72 h, prior to and following IL-6 stimulation. The adhesion capacities of neutrophils to the treated A549 cells, and the expression levels of cluster of differentiation (CD)54 by the epithelial cells were measured. Treatment of the A549 cells with either EtOH or EtP significantly reduced the IL-6-induced release of IL-8. This effect was observed in the pre- and post-stimulatory conditions, which is of therapeutic importance. Similar data was revealed regarding the IL-6-induced neutrophil adhesion to the treated A549 cells, in which pre- and post-treatment with EtOH or EtP decreased the adhesion capacity, however, the results were dependent on the duration of incubation. Incubation durations of 1 and 24 h decreased the adhesion rates of neutrophils to the stimulated A549 cells, however, the reduction was only significant at 72 h post-treatment. The expression of CD54 was reduced only following treatment for 24 h with either EtOH or EtP, prior to IL-6 stimulation. Therefore, EtOH and EtP reduced the inflammatory response of lung epithelial cells, and the potential of EtP to mimic EtOH was observed in the pre- and post-treatment conditions.

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Ethyl pyruvate modulates adhesive and secretory reactions in human lung epithelial cells

Cited by 12 publications

References 21 publications

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells

Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms

Pre- or post-treatment with ethanol and ethyl pyruvate results in distinct anti-inflammatory responses of human lung epithelial cells triggered by interleukin-6

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