Inhibition of FOSL1 alleviates inflammatory injury of otitis media by reducing ferroptosis.

Objectives: Otitis media (OM) is a disease involving inflammation and infection of the middle ear that primarily affects children. Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key regulator in inflammation and various diseases. However, the role of FOSL1 in OM remains largely unknown. Our study aimed to elucidate the function and mechanism of FOSL1 in OM.

Methods: The gene expression dataset was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) from OM mice and control mice were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify potential biological pathways. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were performed to excavate the biological signaling pathways. The OM cell model was induced by Staphylococcus aureus and Bacillus cereus administration. The expression of FOSL1 and ferroptosis-related proteins in OM cell model were determined by western blot. Inflammatory cytokines in cells were detected by qPCR.

Results: DEGs was identified from gene set enrichment (GSE) 49128, 441 genes were up-regulated and 180 were down-regulated. FOSL1 was highly expressed in OM mice. Consistent with the bioinformatic analysis, the expression of FOSL1 in bacterial-induced OM cells was upregulated. Inhibition of FOSL1 via siRNA alleviated the inflammatory response and cell ferroptosis in the OM cell model. The reduced level of inflammatory cytokines and cell ferroptosis induced by FOSL1 inhibition could be rescued by ferroptosis activator erastin.

Conclusion: FOSL1 inhibition could alleviate release of inflammatory cytokines and ferroptosis in the OM cell model.