Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media
Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media
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DOI：
10.1097/mao.0000000000002537
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发表时间：
2020-03-01
影响因子：
2.1
通讯作者：
Nishizaki, Kazunori
中科院分区：
文献类型：
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作者：
Kariya, Shin;Okano, Mitsuhiro;Nishizaki, Kazunori
假设：巨噬细胞移动抑制因子（Macrophage migration inhibitor factor，MMF）在脂多糖诱导的中耳炎中对白细胞介素（interleukin，IL）-1 β和核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor protein 3，NLRP 3）炎性小体的表达起重要作用。背景：NLRP 3炎性体和巨噬细胞移动抑制因子是介导炎症反应的重要分子。然而，NLRP 3炎性体和巨噬细胞迁移抑制因子之间的相互作用尚未得到充分研究。研究方法：野生型小鼠和巨噬细胞移动抑制因子基因缺陷（MIF-/-）小鼠接受经鼓膜注射脂多糖或磷酸盐缓冲盐水。注射后24小时处死小鼠。通过酶联免疫吸附试验测量中耳积液中IL-1 β、NLRP 3、ASC（含有半胱氨酸蛋白酶募集结构域和pyrin结构域的细胞凋亡相关斑点样蛋白）和半胱氨酸蛋白酶-1的浓度。颞骨进行组织学检查和免疫组化。结果如下：在使用野生型小鼠的免疫组织化学研究中，在中耳中由脂多糖诱导的浸润炎性细胞中观察到巨噬细胞移动抑制因子、NLRP 3、ASC和半胱天冬酶-1的阳性染色。与野生型小鼠相比，由脂多糖给药引起的炎症细胞数量在MIF-/-小鼠中显著减少。在脂多糖处理的野生型小鼠中，IL-1 β、NLRP 3、ASC和半胱天冬酶-1的浓度增加。与野生型小鼠相比，具有脂多糖的MIF-/-小鼠具有降低的IL-1 β、NLRP 3、ASC和半胱天冬酶-1水平。结论：巨噬细胞移动抑制因子在IL-1 β和NLRP 3炎性小体的产生中起重要作用。通过调节巨噬细胞移动抑制因子和NLRP 3炎性体来控制炎症可能是中耳炎治疗的新策略。
Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1 beta 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-1 beta, 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-1 beta, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF-/- mice with lipopolysaccharide had decreased levels of IL-1 beta, 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-1 beta 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.