Introduction Inflammation is a defensive response of the organism to irritation which is manifested by redness, swelling, heat, pain and dysfunction. The inflammatory response underlies the role of various diseases. Ferroptosis, a unique modality of cell death, driven by iron-dependent lipid peroxidation, is regulated by multifarious cellular metabolic pathways, including redox homeostasis, iron processing and metabolism of lipids, as well as various signaling pathways associated with diseases. A growing body of evidence suggests that ferroptosis is involved in inflammatory response, and targeting ferroptosis has great prospects in preventing and treating inflammatory diseases. Materials and methods Relevant literatures on ferroptosis, inflammation, inflammatory factors and inflammatory diseases published from January 1, 2010 to now were searched in PubMed database. Conclusion In this review, we summarize the regulatory mechanisms associated with ferroptosis, discuss the interaction between ferroptosis and inflammation, the role of mitochondria in inflammatory ferroptosis, and the role of targeting ferroptosis in inflammatory diseases. As more and more studies have confirmed the relationship between ferroptosis and inflammation in a wide range of organ damage and degeneration, drug induction and inhibition of ferroptosis has great potential in the treatment of immune and inflammatory diseases.

No abstract

Background Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease generally limited to the mucosa and submucosa of the colon. Recent studies suggest that ferroptosis is a novel programmed cell death that may be involved in the process of UC. However, the mechanism of ferroptosis in UC remains to be further investigated. Methods The genes associated with UC and ferroptosis were screened by bioinformatics methods, and a random forest model was constructed to identify the core genes of UC and validated with external data sets. Establishment of dextran sodium sulfate (DSS) induced UC in an animal model in vivo. Interferon (IFN)-γ primed immortalized bone marrow-derived macrophages cells stimulated with Lipopolysaccharides (LPS) inflammation model and LPS-stimulated Caco-2 cells colitis model in vitro were constructed. The potential link between Lipocalin-2 (LCN2) and UC ferroptosis was explored by flow cytometry, Fe2+ assay, Western Blot, gene knockdown, hematoxylin and eosin staining, and immunohistochemistry staining. Results Analysis of differentially expressed genes (DEGs) showed that LCN2 was highly expressed in UC. The protein-protein interaction (PPI) networks showed that ferroptosis-associated DEGs were highly correlated with the immune gene LCN2. The most important gene in the random forest model, LCN2, was identified as a core gene in UC. In the LPS/IFN-γ-induced inflammation model, LCN2 expression was elevated, lipid peroxidation, Fe2+, ACSL4 and COX-2 levels increased, whereas GPX4 and FTH1 expression decreased. Similarly, in the DSS-induced UC mouse model, Occludin, ZO-1, Claudin-1, and GPX4 expression were significantly decreased, but ACSL4 and LCN2 expression were elevated. In addition, the use of Ferrostatin-1 (Fer-1) can significantly reverse its trend. More importantly, silencing of LCN2 suppressed ferroptosis events in both the LPS/IFN-γ-induced inflammation model and the LPS-stimulated colitis model. Conclusion In conclusion, our study demonstrates that LCN2 is a key factor in the regulation of ferroptosis in UC and provides additional evidence for the important role of ferroptosis in UC.