α-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection
α-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection
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DOI：
10.1111/j.1365-2893.2006.00762.x
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发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Simmaco, M.
中科院分区：
文献类型：
--
作者：
Aceti, A.;Mangoni, M. L.;Simmaco, M.
α -防御素基因启动子区域包含一个假定的活化T细胞核因子（NFAT）结合位点，并且已知丙型肝炎病毒（HCV）核心蛋白通过NFAT途径激活白细胞介素(IL)-2基因转录。本研究的目的是研究丙型肝炎病毒是否影响人外周血单核细胞(PBMCs) α -防御素的表达，并评估α -防御素与慢性丙型肝炎患者肝损伤之间的相关性。研究人员招募了90名慢性丙型肝炎患者、30名慢性乙型肝炎患者和25名健康对照者。采用质谱法、酶联免疫吸附法、抗菌活性和mRNA水平对pbmc中的α -防御素进行鉴定和定量。用丙型肝炎病毒核心蛋白、乙型肝炎病毒核心抗原刺激3例患者和对照组的PBMCs，定量α -防御蛋白mrna水平。我们发现HCV核心蛋白在体外激活α -防御素转录。慢性丙型肝炎患者（平均+/- SD = 1.103 +/- 0.765 ng/10(6)个细胞）、慢性乙型肝炎患者（0.53 +/- 0.15）和健康对照组(0.217 +/- 0.09)α -防御素水平差异有统计学意义（P < 0.001）。在慢性丙型肝炎患者中，α -防御素水平和抗菌活性与肝纤维化相关。我们的数据表明HCV诱导α -防御素的表达。α -防御素水平与纤维化进展的高度线性相关使得这些肽的测量成为评估纤维化分期的可靠标记。
The alpha-defensin genes promoter regions contain a putative nuclear factors of activated T cells (NFAT)-binding site and it is known that hepatitis C virus (HCV) core protein activates the interleukin (IL)-2 gene transcription through the NFAT pathway. The aims of this study were to investigate if HCV affects the alpha-defensin expression in peripheral human mononuclear cells (PBMCs) and to evaluate the existence of a correlation between alpha-defensins and liver damage in patients with chronic hepatitis C. Ninety patients with chronic hepatitis C, 30 with chronic hepatitis B and 25 healthy controls were enrolled. alpha-Defensins were identified and quantified in PBMCs by mass spectrometry, enzyme-linked immunosorbent assay, antibacterial activity and mRNA levels. PBMCs from three patients and controls were stimulated with HCV core protein, hepatitis B virus core antigen and the alpha-defensin mRNAs level was quantified. We found that HCV core protein activates in vitro the alpha-defensin transcription. alpha-Defensin levels in patients with chronic hepatitis C (mean +/- SD = 1.103 +/- 0.765 ng/10(6) cells), chronic hepatitis B (0.53 +/- 0.15) and healthy controls (0.217 +/- 0.09) resulted significantly different (P < 0.001). In patients with chronic hepatitis C, the alpha-defensin levels and antibacterial activity correlate with the liver fibrosis. Our data suggest that HCV induces alpha-defensin expression. The high linear correlation of alpha-defensin levels with advancing fibrosis makes the measure of these peptides a reliable marker to evaluate fibrosis stage.