Sensing of commensal organisms by the intracellular sensor NOD1 mediates experimental pancreatitis.
Sensing of commensal organisms by the intracellular sensor NOD1 mediates experimental pancreatitis.
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DOI：
10.1016/j.immuni.2012.05.024
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发表时间：
2012-08-24
期刊：
影响因子：
32.4
通讯作者：
Chiba T
中科院分区：
文献类型：
--
作者：
Tsuji Y;Watanabe T;Kudo M;Arai H;Strober W;Chiba T
细胞内传感器NOD 1具有与多种病原体相关的重要宿主防御功能。在这里，我们表明，这种分子也参与了诱导非感染性胰腺炎，通过其对肠道微生物的反应。高剂量蛙皮素（一种胆囊收缩素受体激动剂）给药诱导的胰腺炎依赖于肠道微生物对NOD 1的刺激。为了分析这种NOD 1活性，我们通过同时给予低剂量的雨蛙肽（其本身不诱导胰腺炎）和FK 156（一种NOD 1的激活剂，其模拟已经突破粘膜屏障的肠道细菌的作用）来诱导胰腺炎。胰腺炎依赖于趋化因子MCP-1的腺泡细胞产生和CCR 2+炎性细胞的胰腺内流入。此外，MCP-1的产生涉及转录因子NF-κB和STAT 3的激活，每一个都需要互补的NOD 1和雨蛙肽信号。这些研究表明，肠道平滑肌通过胰腺腺泡细胞中的NOD 1信号传导使非感染性胰腺炎症成为可能。
The intracellular sensor NOD1 has important host defense functions relating to a variety of pathogens. Here we showed that this molecule also participated in the induction of a non-infectious pancreatitis via its response to commensal organisms. Pancreatitis induced by high-dose cerulein (a cholecystokinin receptor agonist) administration depends on NOD1 stimulation by gut microflora. To analyze this NOD1 activity we induced pancreatitis by simultaneous administration of low-dose of cerulein (that does not itself induce pancreatitis) and FK156, an activator of NOD1 that mimics the effect of gut bacteria that have breached the mucosal barrier. The pancreatitis was dependent on acinar cell production of the chemokine MCP-1 and the intra-pancreatic influx of CCR2+ inflammatory cells. Moreover, MCP-1 production involved activation of the transcription factors NF-κB and STAT3, each requiring complementary NOD1 and cerulein signaling. These studies indicate that gut commensals enable non-infectious pancreatic inflammation via NOD1 signaling in pancreatic acinar cells.
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