ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation

Background: The pathogenesis of inflammatory bowel disease (IBD) is closely associated with the dysfunction of the intestinal epithelial barrier, leading to increased bacterial translocation, leukocyte infiltration, and mucosal injury, which may act as a pivotal or incipient event in the pathophysiology of the disorder. The primary objective of this study is to examine the key genes implicated in IBD and the perturbation of intestinal epithelial cell function. Methods: The genes associated with ferroptosis were identified through the utilization of the Gene Expression Omnibus (GEO) database and the GeneCard database. Additionally, an in vitro model of IBD was established by stimulating Caco-2 cells with lipopolysaccharides (LPSs) to investigate the molecular mechanisms underlying intestinal epithelial cell dysfunction. Results: We discovered evidence that establishes a connection between ferroptosis and the inflammatory responses associated with the development of IBD. This evidence suggests that IBD patients who exhibit an inflammatory response have higher expression of the acyl-CoA synthetase long-chain family member 4 (ACSL4) gene compared to IBD patients without an inflammatory response or healthy individuals. Exposure to LPS at concentrations of 1 or 10 μg/mL resulted in a significant upregulation of ferroptosis-related genes ACSL4, GPX4, and SLC7A11, as well as an increase in ferroptosis biomarkers MDA and a decrease in CAT and GSH-Px levels compared to the control group. Inhibition of ACSL4 using si-ACSL4 or rosiglitazone demonstrated protective effects against LPS-induced ferroptosis and NF-κB-mediated inflammatory response. Conclusion: ACSL4 shows potential as a promising target for ferroptosis in the prevention and treatment of IBD and dysfunction of intestinal epithelial cells.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation ; volume:19 ; number:1 ; year:2024 ; extent:12 ; Open medicine ; 19, Heft 1 (2024) (gesamt 12)

Contributors, Places and Time

• Creator: Lam, Ieng-Hou ; Chan, Chon-In ; Han, Meixia ; Li, Lixuan ; Yu, Hon-Ho

Further information

• DOI: 10.1515/med-2024-0993
• URN: urn:nbn:de:101:1-2409071549065.362689366265
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:23 AM CEST