Department of Infectious Diseases, Huashan Hospital, Shanghai, China.
J Dig Dis. 2011 Apr;12(2):117-24. doi: 10.1111/j.1751-2980.2011.00486.x.
This study aims to measure the expression of toll-like receptors (TLR) in monocyte-derived dendritic cells (MoDC) from chronic severe hepatitis B (CSHB), to assess the contribution of TLRs in CSHB.
Peripheral blood was collected from 40 CSHB patients, 30 chronic hepatitis B (CHB) patients, and 30 healthy individuals who served as healthy controls (HCs). Purified monocytes were isolated by a combination of Histopaque-1.077 and CD14 Microbeads. MoDCs were induced with granulocyte macrophage colony-stimulating factor and interleukin-4 for 6 days from CD14(+) monocytes. The expression of TLRs in MoDC was measured using real-time PCR and flow cytometry.
The expressions of TLR-1, -2, -7 were significantly higher in MoDC of CSHB than that of HCs, of which the level of TLR-3 was decreased. Particularly in CSHB patients, the TLR-3 expression was further decreased compared to CHB patients. In non-survival CSHB patients, TLR-3 level was significantly decreased, while TLR-2 expression was dramatically increased. Linear correlation analysis demonstrated significant correlations between TLR-3 level and disease severity markers (total bilirubin, prothrombin activity, creatinine, white blood cell count, and maximum volume of ascitic fluid) in individual CSHB patients.
TLR-2 and TLR-3 may be involved in the pathogenesis of CSHB, and TLR-3 may influence the prognosis of CSHB.
本研究旨在检测慢性重型乙型肝炎（CSHB）患者单核细胞来源树突状细胞（MoDC）中 Toll 样受体（TLR）的表达，评估 TLR 在 CSHB 中的作用。
收集 40 例 CSHB 患者、30 例慢性乙型肝炎（CHB）患者和 30 例健康个体（健康对照，HCs）的外周血。采用 Histopaque-1.077 和 CD14 Microbeads 联合分离纯化外周血单个核细胞。采用粒细胞巨噬细胞集落刺激因子和白细胞介素-4 从 CD14+单核细胞诱导 MoDC 分化 6 天。采用实时 PCR 和流式细胞术检测 MoDC 中 TLRs 的表达。
CSHB 患者 MoDC 中 TLR-1、TLR-2、TLR-7 的表达明显高于 HCs，其中 TLR-3 的水平降低。特别是在 CSHB 患者中，与 CHB 患者相比，TLR-3 的表达进一步降低。在非生存 CSHB 患者中，TLR-3 水平显著降低，而 TLR-2 表达显著增加。线性相关分析显示，TLR-3 水平与个别 CSHB 患者的疾病严重程度标志物（总胆红素、凝血酶原活动度、肌酐、白细胞计数和最大腹水体积）之间存在显著相关性。
TLR-2 和 TLR-3 可能参与 CSHB 的发病机制，TLR-3 可能影响 CSHB 的预后。
