Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells. (19th March 2021)

• Record Type: Journal Article
• Authors: Mörs, Katharina; Sturm, Ramona; Hörauf, Jason-Alexander; Kany, Shinwan; Cavalli, Paola; Omari, Jazan; Powerski, Maciej; Surov, Alexey; Marzi, Ingo; Nowak, Aleksander J.; Relja, Borna
• Other Names: Zhou Heng Academic Editor.
• Is Part Of: Disease markers. Volume 2021(2021)
• Publication Date: 2021-03-19
• Subjects: Diagnosis -- Periodicals; Biochemical markers -- Periodicals; Pathology -- Periodicals; 616
• DOI: 10.1155/2021/6622701
• Languages: English
• ISSNs: 0278-0240

Abstract

Abstract : Background . In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods . HepG2 cells were stimulated with IL-1 β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF- α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results . In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1 β -induced IL-6 and TNF- α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1 β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1 β -induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion . EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.