Inhibition of FABP4 Ameliorates IL-13-Induced Inflammatory Response and Barrier Dysfunction in Nasal Mucosal Epithelial Cells through the Regulation of Ferroptosis.

This study was conducted to investigate the role and the mechanism of fatty acid-binding protein 4 (FABP4) in allergic rhinitis (AR). To induce AR in vitro, human nasal epithelial cells (hNECs) were treated by interleukin (IL)-13. Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot were used to detect FABP4 expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory level while inflammation-related proteins were detected by western blot. Immunofluorescence (IF) assay was used to detect mucin-5AC (MUC5AC) and zonula occludens-1 (ZO-1) level. The expressions of tight junction proteins were detected by western blot. Lipid reactive oxygen species (ROS) was detected using a BODIPY 581/591 C11 kit and iron level was detected by corresponding assay kits. Ferroptosis-related proteins were detected by western blot. With the goal of investigating the mechanism of FABP4 associated with ferroptosis, cells were pretreated by ferroptosis inducer erastin (30 mM) and rescue experiments were implemented. In this work, FABP4 expression was increased in hNECs treated by IL-13. After FABP4 was knocked down, the inflammation, mucus production, barrier dysfunction and ferroptosis induced by IL-13 in hNECs were all repressed. Nevertheless, erastin pre-treatment partially counteracted the protective role of FABP4 depletion against inflammation, mucus production and barrier dysfunction in IL-13-treated hNECs. In summary, FABP4 deficiency ameliorated IL-13-induced inflammatory response and barrier dysfunction in nasal mucosal epithelial cells through the regulation of ferroptosis.