Inhibition of macrophage migration inhibitory factor alleviates LPS-induced inflammation response of HEI-OC1 cells via suppressing NF-κB signaling

• Published in: Cytokine (Philadelphia, Pa.) Vol. 150; p. 155776
• Main Authors: Zhu, Wenyan, She, Wandong, Gao, Ziwen, Ma, Yongchi, Jin, Xin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2022
• Subjects: Animals; COX2; Inflammation - chemically induced; Intramolecular Oxidoreductases; Lipopolysaccharides - pharmacology; Macrophage Migration-Inhibitory Factors - genetics; Mice; MIF; NF-kappa B - metabolism; NF-κB signaling; PGE2; Phosphatidylinositol 3-Kinases; SSNHL; NF-κB signaling; PGE2; COX2; SSNHL; MIF
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2021.155776

•Augmentation of PGE2 synthesis and COX2 expression in HEI-OC1 cells by LPS.•MIF downregulation leads to decrease in PGE2 synthesis and COX2 expression.•MIF knockdown suppresses the PI3K/AKT/NF-κB pathway in LPS-treated HEI-OC1 cells.•MIF increases PGE2 production and COX2 expression via the NF-κB pathway.•MIF promotes LPS-induced inflammation in HEI-OC1 cells via the NF-κB pathway. Sudden sensorineural hearing loss (SSNHL) is acute and unexplained. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine in several inflammatory diseases. However, its role in SSNHL remains elusive. Lipopolysaccharide (LPS) was used to induce the inflammatory response of murine auditory cells, HEI-OC1. Silencing of MIF in HEI-OC1 cells was achieved by transfection of short hairpin RNA against MIF. 740Y-P and IMD0354 were used to stimulate the PI3K pathway and suppress the NF-κB pathway, respectively. RT-qPCR and western blotting were used to examine MIF and cyclooxygenase 2 (COX2) expression in LPS-treated HEI-OC1 cells. ELISA was employed to assess prostaglandin E2 (PGE2) concentrations. MIF was upregulated in LPS-treated HEI-OC1 cells. MIF knockdown reduced PGE2 synthesis and COX2 expression in LPS-treated HEI-OC1 cells. Moreover, MIF knockdown suppressed activation of the PI3K/AKT and NF-κB pathway in LPS-treated HEI-OC1 cells. Additionally, inhibition of MIF decreased PGE2 production and COX2 expression via inactivation of the NF-κB pathway. Inhibition of MIF alleviated LPS-induced inflammation in HEI-OC1 cells via inactivating the NF-κB signaling, which might provide a better understanding for SSNHL development.