Institute for the Application of Nuclear Energy, INEP, University of Belgrade, Belgrade, Serbia.
Reproduction. 2010 Apr;139(4):789-98. doi: 10.1530/REP-09-0341. Epub 2010 Feb 4.
Interleukin-8 (IL8/CXCL8) is present in decidua and trophoblast, which also expresses the IL8 receptors, CXCR1 and CXCR2. IL8 was shown to stimulate trophoblast migration. Matrix metalloproteinase (MMP)2, MMP9, and integrins alpha(5)beta(1) and alpha(1)beta(1) were found to play important roles in trophoblast invasion. We hypothesized that IL8 would increase this cell migration and invasion by HTR-8/SVneo cells through the activity of MMPs and integrins. Isolated first trimester of pregnancy cytotrophoblast (CT) and HTR-8/SVneo cell line were used. Migration was studied by monolayer wounding test, and invasion by Matrigel invasion test. The effects of IL8 on MMPs and integrin subunit expression were determined in HTR-8/SVneo cells by gelatin zymography and western blot respectively. The results that were obtained showed that exogenous IL8 stimulated HTR-8/SVneo cell migration and invasion. MMP2 and MMP9 levels were stimulated to 182% (P<0.01) and 134% (P<0.01) respectively. Integrin alpha(5) expression was increased to 119% (P<0.05) and integrin beta(1) expression to 173% (P<0.001) of the control values. The data that were obtained show for the first time the sensitivity of the HTR-8/SVneo cells, in addition to isolated first trimester CT, to IL8. Exogenous IL8/CXCL8 increased trophoblast cell migration and invasion, which may be partly attributable to stimulation of MMP2 and MMP9 levels and an increase in integrins. HTR-8/SVneo cell viability and proliferation were also increased.
白细胞介素-8（IL8/CXCL8）存在于蜕膜和滋养层中，滋养层也表达 IL8 受体 CXCR1 和 CXCR2。研究表明，IL8 可刺激滋养层迁移。基质金属蛋白酶（MMP）2、MMP9 和整合素 α5β1 和 α1β1 被发现在滋养层浸润中发挥重要作用。我们假设，IL8 通过 MMP 和整合素的活性增加 HTR-8/SVneo 细胞的这种细胞迁移和侵袭。使用分离的妊娠早期绒毛细胞（CT）和 HTR-8/SVneo 细胞系进行研究。通过单层划痕试验研究迁移，通过 Matrigel 侵袭试验研究侵袭。通过明胶酶谱法和 Western blot 分别确定 IL8 对 HTR-8/SVneo 细胞中 MMP 和整合素亚基表达的影响。结果表明，外源性 IL8 刺激 HTR-8/SVneo 细胞迁移和侵袭。MMP2 和 MMP9 水平分别增加到 182%（P<0.01）和 134%（P<0.01）。整合素 α5 表达增加到对照值的 119%（P<0.05），整合素 β1 表达增加到对照值的 173%（P<0.001）。这些数据首次表明，除了分离的妊娠早期 CT 之外，HTR-8/SVneo 细胞对 IL8 敏感。外源性 IL8/CXCL8 增加了滋养层细胞的迁移和侵袭，这可能部分归因于 MMP2 和 MMP9 水平的刺激以及整合素的增加。HTR-8/SVneo 细胞的活力和增殖也增加。
