Shi Min, Wei Jue, Dong Jinbin, Meng Wenying, Ma Jiali, Wang Ting, Wang Na, Wang Yugang
Department of Gastroenterology, Shanghai Changning Central Hospital, Shanghai 200336, P.R. China.
Mol Med Rep. 2015 Jan;11(1):121-6. doi: 10.3892/mmr.2014.2681. Epub 2014 Oct 16.
Intrahepatic T helper (Th)17 cytokine and serum interleukin (IL)-17 levels in patients with hepatitis B are positively correlated with the progression of liver cirrhosis (LC). IL-35 can significantly inhibit the differentiation of Th17 cells and the synthesis of IL-17. The present study aimed to investigate the function and expression of IL-17 and IL-35 in the blood of patients with hepatitis B‑related LC. The levels of IL-17 and IL-35 in the peripheral blood of 30 patients with chronic hepatitis B (CHB), 79 with LC, 14 with chronic severe hepatitis B (CSHB), and 20 normal controls were detected by ELISA. Quantitative polymerase chain reaction was used to evaluate Epstein-Barr virus-induced gene 3 (EBI3), forkhead box (FOX)P3 and IL-17 mRNA expression levels in peripheral blood mononuclear cells (PBMCs). Western blotting was used to determine protein expression. The liver function of patients and normal controls was measured. EBI3, IL-17 and FOXP3 mRNA expression levels in PBMCs from patients with LC, CHB and CSHB were higher than those in cells from the controls. IL-17 mRNA levels differed significantly according to the Child-Pugh classification and exhibited an upward trend over time in contrast to a downward trend for EBI3 and FOXP3 mRNA. The changes in protein expression in the peripheral blood were consistent with the changes in mRNA expression. Serum IL-17 levels were positively correlated with total bilirubin (TBIL), alanine aminotransferase (ALT) and Child-Pugh grade, and were negatively correlated with albumin. These observed differences were significant. Serum IL-35 levels were negatively correlated with albumin, but not with Child-Pugh grade, ALT and TBIL. IL-17 and IL-35 may be critically involved in the pathogenesis of hepatitis B-related LC.
乙型肝炎患者肝内辅助性T细胞(Th)17细胞因子及血清白细胞介素(IL)-17水平与肝硬化(LC)进展呈正相关。IL-35可显著抑制Th17细胞分化及IL-17合成。本研究旨在探讨IL-17和IL-35在乙型肝炎相关LC患者血液中的功能及表达情况。采用酶联免疫吸附测定法(ELISA)检测30例慢性乙型肝炎(CHB)患者、79例LC患者、14例慢性重型乙型肝炎(CSHB)患者及20例正常对照者外周血中IL-17和IL-35水平。运用定量聚合酶链反应评估外周血单个核细胞(PBMC)中EB病毒诱导基因3(EBI3)、叉头框(FOX)P3及IL-17 mRNA表达水平。采用蛋白质印迹法测定蛋白表达。检测患者及正常对照者的肝功能。LC、CHB及CSHB患者PBMC中EBI3、IL-17及FOXP3 mRNA表达水平高于对照组细胞。IL-17 mRNA水平根据Child-Pugh分级有显著差异,且随时间呈上升趋势,而EBI3和FOXP3 mRNA呈下降趋势。外周血中蛋白表达变化与mRNA表达变化一致。血清IL-17水平与总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)及Child-Pugh分级呈正相关,与白蛋白呈负相关。这些差异具有统计学意义。血清IL-35水平与白蛋白呈负相关,但与Child-Pugh分级、ALT及TBIL无关。IL-17和IL-35可能在乙型肝炎相关LC发病机制中起关键作用。