Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.
Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.
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DOI：
10.1371/journal.pone.0073205
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nishizono A
中科院分区：
文献类型：
--
作者：
Nakano S;Ikebe E;Tsukamoto Y;Wang Y;Matsumoto T;Mitsui T;Yahiro T;Inoue K;Kawazato H;Yasuda A;Ito K;Yokoyama S;Takahashi N;Hori M;Shimada T;Moriyama M;Kubota T;Ono K;Fujibuchi W;Jeang KT;Iha H;Nishizono A
Tax 1结合蛋白1（Tax 1bp 1）通过其催化配偶体A20编辑靶分子的泛素化来负调控NF-κB。基因工程TAX 1BP 1缺陷（KO）小鼠在多个器官中发展出年龄依赖性炎症结构，表现为瓣膜炎或皮炎，并过早死亡。对TAX 1BP 1-KO小鼠（8周龄和16周龄）的二尖瓣进行激光捕获解剖和基因表达微阵列分析，发现与野生型相比有588个基因转录改变。SAA 3（血清淀粉样蛋白A3）、CHI 3L 1、HP、IL 1B和SPP 1/OPN分别被诱导1，180、361、187、122和101倍。WIF 1（Wnt抑制因子1）表现出11倍的减少。再次证实了强烈的Saa 3染色和显著的I-κBα减少，在该区域可见大量炎性淋巴细胞浸润和水肿形成。抗生素诱导的“无菌”状态或额外的MyD 88缺陷显著改善了TAX 1BP 1-KO小鼠的炎症病变。这些病理状况，我们称之为“假性感染性心内膜炎”，是由通常无害的肠道微生物群引起的。这一实验结果提出了一种新的机制之间的联系，内皮炎症引起的泛素重塑免疫调节剂和致命的心功能不全。
Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced ‘germ free’ status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.5
作者：
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影响因子：
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