Ethanol decreases inflammatory response in human lung epithelial cells by inhibiting the canonical NF-kB-pathway
- 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.
Author: | Katharina MörsGND, Jason-Alexander HöraufORCiDGND, Shinwan Salah KanyORCiDGND, Nils WagnerORCiDGND, Ramona SturmGND, Mathias WoschekGND, Mario Perl, Ingo MarziORCiDGND, Borna ReljaORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-450837 |
DOI: | https://doi.org/10.1159/000480313 |
ISSN: | 1421-9778 |
ISSN: | 1015-8987 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28848184 |
Parent Title (German): | Cellular physiology and biochemistry |
Publisher: | Karger |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Year of Completion: | 2017 |
Year of first Publication: | 2017 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/11/15 |
Tag: | NF-ĸB; alcohol; canonical; inflammation; intoxication; lung; non-canonical; trauma |
Volume: | 43 |
Page Number: | 14 |
First Page: | 17 |
Last Page: | 30 |
Note: | This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). |
HeBIS-PPN: | 42789199X |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Open-Access-Publikationsfonds: | Medizin |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |