Jovanović M, Vićovac L
Institute for Application of Nuclear Energy INEP, University of Belgrade, Banatska 31b, 11080 Belgrade-Zemun, Serbia.
Placenta. 2009 Apr;30(4):320-8. doi: 10.1016/j.placenta.2009.01.013. Epub 2009 Feb 28.
Interleukin-6 (IL-6) is present in human endometrium throughout menstrual cycle and in pregnancy. Trophoblast also expresses IL-6. IL-6R and its associated signal transducer gp130 were found in trophoblast as well. IL-6 is generally assumed to be relevant for trophoblast invasion. This study was undertaken to determine influence of endogenous and externally added IL-6 on invasion and migration of first trimester of pregnancy trophoblast in vitro. Integrins alpha(5)beta(1) and alpha(1)beta(1) have been shown to play an important role in trophoblast invasion and the effect of IL-6 on the expression of these integrin subunits was studied. We are showing that in both isolated first trimester of pregnancy cytotrophoblast (CTB) and HTR-8/SVneo cell line IL-6 and IL-6R are present. The effect on migration was studied using cell wounding and migration test on HTR-8/SVneo cells. Effect of IL-6 and function blocking anti-IL-6 antibody in Matrigel invasion tests was studied on both cell types. The effect of IL-6 on integrin subunit expression was determined by cell-based ELISA and Western blot on HTR-8/SVneo cells. The results obtained show that exogenous IL-6 has stimulatory effect on cell migration in HTR-8/SVneo and invasion by both cell types. Function blocking anti-IL-6 inhibited unstimulated invasion by isolated first trimester cytotrophoblast and both cell migration and invasion in unstimulated HTR-8/SVneo. Integrin alpha(5) expression was stimulated by IL-6 to 134% (p<0.05), alpha(1) to 135% (p<0.005), and beta(1) to 134% (p<0.001) of control in cell-based ELISA, but also in Western blot. The data obtained show for the first time sensitivity of extravillous trophoblast cell line HTR-8/SVneo to IL-6, in addition to isolated first trimester cytotrophoblast. We conclude that both exogenous and endogenous IL-6 stimulate trophoblast cell migration and invasion, which may be partly attributable to stimulation of expression of the studied integrin subunits.
白细胞介素-6（IL-6）在人类子宫内膜的整个月经周期及孕期均有表达。滋养层细胞也表达IL-6。在滋养层细胞中还发现了IL-6受体及其相关信号转导分子gp130。一般认为IL-6与滋养层细胞的侵袭有关。本研究旨在确定内源性和外源性添加的IL-6对孕早期滋养层细胞体外侵袭和迁移的影响。整合素α(5)β(1)和α(1)β(1)已被证明在滋养层细胞侵袭中起重要作用，因此研究了IL-6对这些整合素亚基表达的影响。我们发现，在分离的孕早期细胞滋养层细胞（CTB）和HTR-8/SVneo细胞系中均存在IL-6和IL-6受体。使用细胞划痕和迁移试验研究了其对HTR-8/SVneo细胞迁移的影响。在基质胶侵袭试验中研究了IL-6和功能阻断性抗IL-6抗体对两种细胞类型的影响。通过基于细胞的ELISA和Western印迹法测定了IL-6对HTR-8/SVneo细胞整合素亚基表达的影响。所得结果表明，外源性IL-6对HTR-8/SVneo细胞的迁移以及两种细胞类型的侵袭均有刺激作用。功能阻断性抗IL-6抑制了分离的孕早期细胞滋养层细胞的基础侵袭以及未刺激的HTR-8/SVneo细胞的迁移和侵袭。在基于细胞的ELISA中，IL-6刺激整合素α(5)的表达至对照的134%（p<0.05），α(1)至135%（p<0.005），β(1)至134%（p<0.001），Western印迹结果也是如此。所得数据首次表明，除了分离的孕早期细胞滋养层细胞外，绒毛外滋养层细胞系HTR-8/SVneo对IL-6敏感。我们得出结论，外源性和内源性IL-6均刺激滋养层细胞的迁移和侵袭，这可能部分归因于对所研究的整合素亚基表达的刺激。
