Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.
Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.
复制标题
DOI：
10.3390/ijms17111878
复制
发表时间：
2016-11-10
影响因子：
5.6
通讯作者：
Crespo J
中科院分区：
文献类型：
--
作者：
Arias-Loste MT;Iruzubieta P;Puente Á;Ramos D;Santa Cruz C;Estébanez Á;Llerena S;Alonso-Martín C;San Segundo D;Álvarez L;López Useros A;Fábrega E;López-Hoyos M;Crespo J
目前的证据表明，肠道生态失调驱动肥胖和非酒精性脂肪肝（NAFLD）的发病机制。Toll样受体2（TLR 2）和TLR 6特异性识别革兰氏阳性菌的组分。尽管TLR 2在NAFLD发病机制中具有潜在意义，但TLR 6的作用尚未得到解决。我们的目的是研究TLR 6在肥胖相关NAFLD中的潜在作用。对40例接受减肥手术的病态肥胖患者进行了前瞻性研究。通过流式细胞术评估外周血单核细胞（PBMC）上TLR 2和TLR 6的细胞表面表达。将新鲜分离的单核细胞与特异性TLR 2/TLR 6激动剂一起培养，并通过流式细胞术测定细胞因子的细胞内产生。在肝活检中，通过免疫组织化学和使用RT-qPCR的细胞因子基因表达分析TLR 2和TLR 6的表达。非酒精性脂肪性肝炎（NASH）患者PBMC中的TLR 6表达显著高于单纯性脂肪变性患者。在有小叶炎症的患者中，响应于TLR 2/TLR 6刺激的促炎细胞因子的产生也显著更高。与正常肝组织学相比，NAFLD患者的肝细胞TLR 6表达增加，但TLR 2表达不增加。病态肥胖患者外周TLR 6的表达和活性失调可以反映肝脏炎症事件，这些事件是众所周知的肥胖相关NASH发病机制的驱动因素。此外，TLR 6在NAFLD患者的肝细胞中也显著过表达。因此，TLR 6表达失调可能会增强TLR 2介导的肝脏炎症在NAFLD发病机制，也作为一个潜在的外周生物标志物肥胖相关的NASH。
Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.
登录
查看更多内容
DOI：
10.1111/j.1530-0277.2011.01487.x
发表时间：
2011-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Inokuchi S;Tsukamoto H;Park E;Liu ZX;Brenner DA;Seki E
通讯作者：
Seki E
DOI：
10.1152/ajpgi.00163.2009
发表时间：
2011-03-01
影响因子：
4.5
作者：
Csak, Timea;Velayudham, Arumugam;Szabo, Gyongyi
通讯作者：
Szabo, Gyongyi
影响因子：
8.2
作者：
Ehses, J. A.;Meier, D. T.;Donath, Marc Y.
通讯作者：
Donath, Marc Y.
影响因子：
3.5
作者：
Takeuchi, O;Kawai, T;Akira, S
通讯作者：
Akira, S
影响因子：
13.5
作者：
Chalasani, N
通讯作者：
Chalasani, N