Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kappa B-Pathway

Moers K, Hoerauf JA, Kany S, Wagner N, Sturm R, Woschek M, Marzi I, Relja B, Perl M (2017)

Publication Status: Published

Publication Type: Journal article

Publication year: 2017

Journal

Cellular Physiology and Biochemistry Karger

Publisher: KARGER

Book Volume: 43

Pages Range: 17-30

Journal Issue: 1

DOI: 10.1159/000480313

Abstract

Background/Aims: Alcohol (ethanol, EtOH) as significant contributor to traumatic injury is linked to suppressed inflammatory response, thereby influencing clinical outcomes. Alcohol-induced immune-suppression during acute inflammation (trauma) was linked to nuclear factor-kappaB (NF-kappa B). Here, we analyzed alcohol's effects and mechanisms underlying its influence on NF-kappa B-signaling during acute inflammation in human lung epithelial cells. Methods: A549-cells were stimulated with interleukin (IL)-1 beta, or sera from trauma patients (TP) or healthy volunteers, with positive/negative blood alcohol concentrations (BAC), and subsequently exposed to EtOH (170 Mm, 1h). IL-6-release and neutrophil adhesion to A549 were analyzed. Specific siRNA-NIK mediated downregulation of non-canonical, and IKK-NBD-inhibition of canonical NF-kappa B signaling were performed. Nuclear levels of activated p50 and p52 NF-kappa B-subunits were detected using TransAm ELISA. Results: Both stimuli significantly induced IL-6-release (39.79 +/- 4.70 vs. 0.58 +/- 0.8 pg/ml) and neutrophil adhesion (132.30 +/- 8.80 vs. 100% control, p < 0.05) to A549-cells. EtOH significantly decreased IL-6-release (22.90 +/- 5.40, p < 0.05) and neutrophil adherence vs. controls (105.40 +/- 14.5%, p < 0.05). IL-1 beta-induced significant activation of canonical/p50 and non-canonical/p52 pathways. EtOH significantly reduced p50 (34.90 +/- 23.70 vs. 197.70 +/- 36.43, p < 0.05) not p52 activation. Inhibition of canonical pathway was further increased by EtOH (less p50-activation), while p52 remained unaltered. Inhibition of non-canonical pathway was unchanged by EtOH. Conclusion: Here, alcohol's anti-inflammatory effects are mediated via decreasing nuclear levels of activated p50-subunit and canonical NF-kappa B signaling pathway. (C) 2017 The Author(s) Published by S. Karger AG, Basel

Authors with CRIS profile

Mario Perl

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Berufsgenossenschaftliche Unfallklinik (BGU) Murnau DE Germany (DE)

How to cite

APA:

Moers, K., Hoerauf, J.-A., Kany, S., Wagner, N., Sturm, R., Woschek, M.,... Perl, M. (2017). Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kappa B-Pathway. Cellular Physiology and Biochemistry, 43(1), 17-30. https://doi.org/10.1159/000480313

MLA:

Moers, Katharina, et al. "Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kappa B-Pathway." Cellular Physiology and Biochemistry 43.1 (2017): 17-30.

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