The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media.
The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media.
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DOI：
10.1177/1753425914526074
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发表时间：
2015-02
期刊：
影响因子：
3.2
通讯作者：
Wasserman SI
中科院分区：
文献类型：
--
作者：
Kurabi A;Lee J;Wong C;Pak K;Hoffman HM;Ryan AF;Wasserman SI
本研究旨在了解炎症小体和IL-1β活化在中耳炎（OM）中的作用。我们使用基因微阵列和小鼠急性OM模型检测了野生型（WT）小鼠中耳（ME）对不可分型流感嗜血杆菌（NTHi）的反应。炎症小体基因NOD结构域样受体家族成员的表达在NTHi感染ME的早期显著上调，可能激活特定的下游调节级联反应，促进OM期间观察到的增殖性炎症反应。炎性小体靶点前形态IL-1β和IL-18的表达也上调。为了评估炎症小体介导的细胞因子成熟的作用，我们在Asc−/−缺陷小鼠中检测了nthi诱导的OM，并与WT小鼠进行了比较。缺乏Asc基因的小鼠在ME中几乎没有IL-1β成熟，白细胞募集和浸润减少，巨噬细胞对NTHi的吞噬减少。这些炎症缺陷与Asc - / -小鼠ME粘膜上皮增生的程度和持续时间的增加有关，也与它们ME细菌清除的延迟有关。这些数据表明炎症小体和细胞因子加工在OM的过程和解决中起重要作用。
This study was designed to understand the contribution of the inflammasome and IL-1β activation in otitis media (OM). We examined the middle ear (ME) response to non-typeable Haemophilus influenzae (NTHi) in wild type (WT) mice using gene microarrays and a murine model of acute OM. Expression of members of the NOD domain-like receptor family of inflammasome genes was significantly up-regulated early in NTHi infection of the ME, potentially activating specific downstream regulatory cascades that contribute to the proliferative inflammatory response observed during OM. Expression of the pro-forms of the inflammasome targets IL-1β and IL-18 were also up-regulated. To evaluate the role of inflammasome-mediated cytokine maturation, NTHi-induced OM was examined in Asc−/−-deficient mice and compared with that seen in WT mice. Mice lacking the Asc gene showed near absence of IL-1β maturation in the ME and a reduction in leukocyte recruitment and infiltration to the cavity, and their macrophages exhibited reduced phagocytosis of NTHi. These inflammatory defects were linked to an increase in the degree and duration of mucosal epithelial hyperplasia in the ME of Asc−/− mice, as well as a delay in bacterial clearance from their MEs. These data demonstrate an important role for the inflammasome and cytokine processing in the course and resolution of OM.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
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作者：
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通讯作者：
Mueller, Anne
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作者：
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影响因子：
4.5
作者：
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通讯作者：
Brown SD