start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=3 article-no= start-page=364 end-page=370 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202003 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1ƒÀ 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-1ƒÀ, 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-1ƒÀ, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF?/? mice with lipopolysaccharide had decreased levels of IL-1ƒÀ, 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-1ƒÀ 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. en-copyright= kn-copyright= en-aut-name=KariyaShin en-aut-sei=Kariya en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkanoMitsuhiro en-aut-sei=Okano en-aut-mei=Mitsuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ZhaoPengfei en-aut-sei=Zhao en-aut-mei=Pengfei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MaedaYukihide en-aut-sei=Maeda en-aut-mei=Yukihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KataokaYuko en-aut-sei=Kataoka en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HigakiTakaya en-aut-sei=Higaki en-aut-mei=Takaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakiharaSeiichiro en-aut-sei=Makihara en-aut-mei=Seiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NishihiraJun en-aut-sei=Nishihira en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TachibanaTomoyasu en-aut-sei=Tachibana en-aut-mei=Tomoyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishizakiKazunori en-aut-sei=Nishizaki en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Otolaryngology?Head and Neck Surgery, Kagawa Rosai Hospital kn-affil= affil-num=8 en-affil=Department of Medical Bioinformatics, Hokkaido Information University kn-affil= affil-num=9 en-affil=Departments of Otolaryngology, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=10 en-affil=Department of Otolaryngology?Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Cytokine kn-keyword=Cytokine en-keyword=Infection kn-keyword=Infection en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Interleukin kn-keyword=Interleukin en-keyword=NOD-like receptor kn-keyword=NOD-like receptor en-keyword=Toll-like receptor kn-keyword=Toll-like receptor END