TY - JOUR
T1 - Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media
AU - Kariya, Shin
AU - Okano, Mitsuhiro
AU - Zhao, Pengfei
AU - Maeda, Yukihide
AU - Kataoka, Yuko
AU - Higaki, Takaya
AU - Makihara, Seiichiro
AU - Nishihira, Jun
AU - Tachibana, Tomoyasu
AU - Nishizaki, Kazunori
N1 - Funding Information:
This work was supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science, and Technology of Japan) (Grant Numbers JP17K11329).
Publisher Copyright:
© 2019, Otology & Neurotology, Inc.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Hypothesis:Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β 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 24hours after the injection. Concentrations of IL-1β, 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-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF-/- mice with lipopolysaccharide had decreased levels of IL-1β, 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-1β 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.
AB - Hypothesis:Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β 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 24hours after the injection. Concentrations of IL-1β, 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-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF-/- mice with lipopolysaccharide had decreased levels of IL-1β, 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-1β 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.
KW - Cytokine
KW - Infection
KW - Inflammation
KW - Interleukin
KW - NOD-like receptor
KW - Toll-like receptor
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U2 - 10.1097/MAO.0000000000002537
DO - 10.1097/MAO.0000000000002537
M3 - Article
C2 - 31821259
AN - SCOPUS:85079203856
SN - 1531-7129
VL - 41
SP - 364
EP - 370
JO - American Journal of Otology
JF - American Journal of Otology
IS - 3
ER -