Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media.

ABSTRACT

HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1ß and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. BACKGROUND: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. METHODS: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1ß, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. RESULTS: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF mice as compared with the wild-type mice. The concentrations of IL-1ß, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF mice with lipopolysaccharide had decreased levels of IL-1ß, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. CONCLUSION: Macrophage migration inhibitory factor has an important role in the production of IL-1ß and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.