Molecular pathological examination of valvulitis developed in TAX1BP1 deficient mice.

Tax 1结合蛋白1（Tax 1bp 1）通过与其催化配偶体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）表现出1，180倍诱导（FI），CHI 3L 1（361-FI），HP（187-FI），IL 1B（122-FI）和SPP 1/OPN（101-FI）。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，以及该区域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 with 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) exhibited a 1,180-fold induction (FI), CHI3L1(361-FI), HP(187-FI), IL1B(122-FI) and SPP1/OPN(101-FI). 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 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.