TY  - JOUR
A1  - Mörs, Katharina
A1  - Hörauf, Jason-Alexander
A1  - Kany, Shinwan Salah
A1  - Wagner, Nils
A1  - Sturm, Ramona
A1  - Woschek, Mathias
A1  - Perl, Mario
A1  - Marzi, Ingo
A1  - Relja, Borna
T1  - Ethanol decreases inflammatory response in human lung epithelial cells by inhibiting the canonical NF-kB-pathway
T2  - Cellular physiology and biochemistry
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.
KW  - inflammation
KW  - trauma
KW  - alcohol
KW  - intoxication
KW  - NF-ĸB
KW  - canonical
KW  - non-canonical
KW  - lung
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45083
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-450837
SN  - 1421-9778
SN  - 1015-8987
N1  - This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
VL  - 43
SP  - 17
EP  - 30
PB  - Karger
CY  - Basel
ER  -