Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist.
Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist.
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DOI：
10.1111/omi.12089
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发表时间：
2015-06
影响因子：
3.7
通讯作者：
Scott DA
中科院分区：
文献类型：
--
作者：
Hutcherson JA;Bagaitkar J;Nagano K;Yoshimura F;Wang H;Scott DA
牙周病是半普遍存在的，由慢性斑块诱导的炎症引起。牙龈卟啉单胞菌（Porphyromonas gingivalis）是一种重要的牙周致病菌，其55 kDa的免疫显性RagB外膜蛋白被认为有助于营养物质的转运。然而，RagB和先天反应之间的潜在相互作用尚未得到研究。我们确定RagB暴露导致原代人单核细胞中编码促炎介质（IL-1α、IL-1β、IL-6、IL-8和CCL 2;所有，p < 0.05）的多种基因的差异和剂量相关表达，以及TNF和IL-8的分泌，但不导致IFN-γ或IL-12的分泌。Rag B是一种TLR 2和TLR 4激动剂，可激活STAT 4和NFκB信号传导。同样，ΔragB突变体也表现出降低的炎症能力，这是由ragB互补拯救的。这些结果表明，RagB elevates一个主要的促炎症反应，在原代人单核细胞，因此，可能发挥重要作用的牙周炎和全身后遗症的病因。
Periodontal diseases are semi-ubiquitous and caused by chronic, plaque-induced inflammation. The 55kDa immunodominant RagB outer membrane protein of Porphyromonas gingivalis, a keystone periodontal pathogen, has been proposed to facilitate nutrient transport. However, potential interactions between RagB and the innate response have not been examined. We determined that RagB exposure led to the differential and dose-related expression of multiple genes encoding pro-inflammatory mediators (IL-1α, IL-1β, IL-6, IL-8 and CCL2; all, p < 0.05) in primary human monocytes and to the secretion of TNF and IL-8, but not IFN-γ or IL-12. RagB was shown to be a TLR2 and TLR4 agonist that activated STAT4 and NFκB signaling. In keeping, a ΔragB mutant similarly exhibited reduced inflammatory capacity which was rescued by ragB complementation. These results suggest that RagB elicits a major pro-inflammatory response in primary human monocytes and, thus, could play an important role in the etiology of periodontitis and systemic sequelae.