Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C-associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma
Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C-associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma
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DOI：
10.1158/1078-0432.ccr-06-0154
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发表时间：
2006-08-01
影响因子：
11.5
通讯作者：
Spengler, Ulrich
中科院分区：
文献类型：
--
作者：
Feldmann, Georg;Nischalke, Hans Dieter;Spengler, Ulrich
目的：慢性丙型肝炎有发生混合冷球蛋白血症 (MC) 和 B 细胞非霍奇金淋巴瘤 (B-NHL) 的风险，可能是因为病毒抗原通过细胞外模式识别受体 (PRR) 刺激宿主的炎症反应。为了阐明这个问题，我们研究了 PRR 对丙型肝炎病毒 (HCV) 蛋白的识别是否与 HCV 相关 MC 或 B-NHL 的发病机制有关。 实验设计：将 HCV 相关 B-NHL 患者 (n = 12)、MC (n = 14)、无并发症丙型肝炎 (n = 12) 和健康志愿者 (n = 12) 的外周血单核细胞与重组 HCV 一起孵育蛋白质 E2、核心和 NS3，用于研究细胞因子产生的诱导、B 细胞增殖的刺激和免疫球蛋白的分泌。此外，通过ELISA测定血清白细胞介素6(IL-6)水平。结果：HCV核心是唯一研究的蛋白，它诱导CD14(+)细胞产生IL-6和IL-8。 IL-6 诱导通过 Toll 样受体 2 (TLR2) 介导，并导致体外 B 细胞增殖增加。与健康对照相比，各组HCV感染者单核细胞上TLR2表达和IL-6血清浓度均升高，且在MC中最高（P < 0.05）。结论：HCV核心蛋白刺激TLR2增加IL-6分泌可能在丙型肝炎相关MC和B-NHL的发病机制中发挥作用。
Purpose: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non - Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL.Experimental Design: Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA.Results: HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05).Conclusions: Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C - associated MC and B-NHL.