Cutting edge:: ASC mediates the induction of multiple cytokines by Porphyromonas gingivalis via caspase-1-dependent and -independent pathways
Cutting edge:: ASC mediates the induction of multiple cytokines by Porphyromonas gingivalis via caspase-1-dependent and -independent pathways
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DOI：
10.4049/jimmunol.177.7.4252
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Ting, Jenny Pan-Yun
中科院分区：
文献类型：
--
作者：
Taxman, Debra J.;Zhang, Jinghua;Ting, Jenny Pan-Yun
牙龈卟啉单胞菌（Pg）是慢性牙周炎的主要病原体。Pg引起的组织破坏部分来自于通过TLR 2信号传导诱导宿主炎症反应。这项工作研究了与糖尿病相关的斑点样蛋白的作用，该蛋白含有半胱天冬酶募集结构域（ASC），这是一种对M介导的半胱天冬酶-1活化很重要的衔接分子。结果表明，ASC水平在用Pg感染人THP 1单核细胞后是稳定的，但在细胞因子诱导后降低。使用短发夹RNA，我们证明了ASC在诱导IL-1 β的TLR 2，4，和5激动剂，活大肠杆菌CA，和PG。诱导IL-6，IL-8，IL-10，和TNF也需要ASC，但这种诱导不受IL-1受体拮抗剂或caspase-1抑制剂抑制。U937中的类似结果表明这些发现具有广泛的适用性。PG感染的ASC敲低THP 1细胞表现出降低的转录水平和NF-κ B活化。这些结果表明，ASC在细胞因子诱导的Pg参与caspase-1依赖和非依赖机制的作用。
Porphyromonas gingivalis (Pg) is a major etiologic agent for chronic periodontitis. Tissue destruction by Pg results partly from induction of host inflammatory responses through TLR2 signaling. This work examines the role of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), an adaptor molecule important for M-mediated caspase-1 activation. Results demonstrate that ASC levels are stable upon infection of human THP1 monocytic cells with Pg but decrease after cytokine induction. Using short hairpin RNA, we demonstrate an essential role for ASC in induction of IL-1 beta by TLR2, 4, and 5 agonists, live Escherichia CA, and Pg. Induction of IL-6, IL-8 IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1 receptor antagonist or caspase-1 inhibitor. Similar results in U937 indicate broad applicability of these findings. Pg-infected ASC knockdown THP1 cells exhibit reduced transcript levels and NF-kappa B activation. These results suggest a role for ASC in cytokine induction by Pg involving both caspase-1-dependent and -independent mechanisms.