Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway
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Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway. / Mörs, Katharina; Hörauf, Jason-Alexander; Kany, Shinwan; Wagner, Nils; Sturm, Ramona; Woschek, Mathias; Perl, Mario; Marzi, Ingo; Relja, Borna.
in: CELL PHYSIOL BIOCHEM, Jahrgang 43, Nr. 1, 2017, S. 17-30.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway
AU - Mörs, Katharina
AU - Hörauf, Jason-Alexander
AU - Kany, Shinwan
AU - Wagner, Nils
AU - Sturm, Ramona
AU - Woschek, Mathias
AU - Perl, Mario
AU - Marzi, Ingo
AU - Relja, Borna
N1 - © 2017 The Author(s). Published by S. Karger AG, Basel.
PY - 2017
Y1 - 2017
N2 - 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-ĸB). Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells.METHODS: A549-cells were stimulated with interleukin (IL)-1β, 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-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-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-1β-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-ĸB signaling pathway.
AB - 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-ĸB). Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells.METHODS: A549-cells were stimulated with interleukin (IL)-1β, 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-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-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-1β-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-ĸB signaling pathway.
KW - A549 Cells
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Cell Adhesion/drug effects
KW - Epithelial Cells/cytology
KW - Ethanol/pharmacology
KW - Female
KW - Humans
KW - I-kappa B Kinase/metabolism
KW - Interleukin-1beta/pharmacology
KW - Interleukin-6/metabolism
KW - Lung/cytology
KW - Male
KW - Middle Aged
KW - NF-kappa B/metabolism
KW - Neutrophils/cytology
KW - Protein-Serine-Threonine Kinases/antagonists & inhibitors
KW - RNA Interference
KW - Signal Transduction/drug effects
KW - Wounds and Injuries/pathology
KW - Young Adult
U2 - 10.1159/000480313
DO - 10.1159/000480313
M3 - SCORING: Journal article
C2 - 28848184
VL - 43
SP - 17
EP - 30
JO - CELL PHYSIOL BIOCHEM
JF - CELL PHYSIOL BIOCHEM
SN - 1015-8987
IS - 1
ER -
