Increased cell proliferation of mouse fibroblast NIH-3T3 in vitro induced by excretory/secretory product(s) from Opisthorchis viverrini
Increased cell proliferation of mouse fibroblast NIH-3T3 in vitro induced by excretory/secretory product(s) from Opisthorchis viverrini
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DOI：
10.1017/s0031182004005815
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发表时间：
2004-10-01
期刊：
影响因子：
2.4
通讯作者：
Wongkham, S
中科院分区：
文献类型：
--
作者：
Thuwajit, C;Thuwajit, P;Wongkham, S
间日圆锥虫的感染是胆管癌的一个重要危险因素。然而，这种寄生虫参与致癌的机制尚不清楚。除了通过直接接触黄氏嗜血杆菌对胆管上皮细胞的直接损伤外，寄生虫释放的排泄/分泌产物(S)可能在这一过程中发挥重要作用。因此，我们用非接触共培养技术研究了成纤维细胞系NIH-3T3对青海乳杆菌释放的ES产物(S)的反应。在该培养体系中，上室寄生虫与培养板下室的NIH-3T3细胞无直接接触。结果表明，在含0%或10%小牛血清的非接触性共培养条件下，NIH-3T3细胞的增殖明显高于无寄生虫培养的NIH-3T3细胞。ES产物(S)通过刺激磷酸化视网膜母细胞瘤和细胞周期蛋白D1的表达来促进细胞增殖，这两个蛋白是驱动细胞通过细胞周期的G1/S转换点的关键蛋白。这导致细胞被诱导进入细胞周期的S期。ES产物(S)还改变了NIH-3T3细胞的形态，使其呈折射状和窄窄状，使细胞能够在有限的培养区域内增殖。这是我们第一次证明了生食弧菌ES产物(S)诱导的细胞增殖增加，这一发现可能有助于阐明产生菌ES产物(S)在胆管癌变过程中如何影响人胆管上皮细胞。
Infection by Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. However, the mechanism by which the parasite is involved in carcinogenesis is not clear. In addition to the direct damage of the bile duct epithelium via direct contact with O. viverrini, the excretory/secretory (ES) product(S) released from the parasites may play important roles in this process. We therefore investigated the responses of a fibroblast cell line, NIH-3T3, to ES product(s) released from O. viverrini by using a non-contact co-culture technique. In this Culture system, the parasites in the upper chamber had no direct contact with the NIH-3T3 cells in the lower chamber of the Culture plate. The results indicated a marked increase in NIH-3T3 cell proliferation in the non-contact co-culture condition with either 0% or 10 % calf serum in the medium compared with that without parasites. ES product(S) increased cell proliferation by stimulating the expression of phosphorylated retinoblastoma (pRB) and cyclin D1, the key proteins in driving cells through the G1/S transition point of the cell cycle. This led to the induction of cells going into the S-phase of the cell cycle. ES product(s) also changed the morphology of NIH-3T3 cells to a refractive and narrow shape, which allowed the cells to proliferate in the limited culture area. For the first time, we have been able to demonstrate increased cell proliferation induced by the ES product(s) from O. viverrini; this finding may clarify how O. viverrini ES product(s) affect human bile duct epithelium during cholangiocarcinogenesis.