Tocilizumab Inhibits Interleukin-6-Mediated Matrix Metalloproteinase-2 and-9 Secretions from Human Amnion Cells in Preterm Premature Rupture of Membranes
Tocilizumab Inhibits Interleukin-6-Mediated Matrix Metalloproteinase-2 and-9 Secretions from Human Amnion Cells in Preterm Premature Rupture of Membranes
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DOI：
10.1159/000229021
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发表时间：
2009-01-01
影响因子：
2.1
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
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作者：
Mano, Yukio;Shibata, Kiyosumi;Kikkawa, Fumitaka
背景/目的：在本研究中，我们调查了参与炎症性白细胞介素（IL）-6诱导的基质金属蛋白酶（MMP）的表达和抑制MMP分泌的羊膜上皮细胞托珠单抗。研究方法：为了探讨MMP表达的作用，免疫组化染色进行了使用从10例早产胎膜早破（PPROM）和10例接受非分娩剖宫产的患者获得的膜。我们还研究了炎症细胞因子对人羊膜细胞MMP表达的调节作用。结果：MMP-2和MMP-9在PPROM中的表达明显高于正常对照组。用10（-8）或10（-7）M IL-6或肿瘤坏死因子（TNF）-α处理培养的WISH和原代羊膜上皮细胞明显增加MMP-2和-9的分泌。与对照组相比，用10（-8）M TNF-α或IL-6治疗分别显著增加了WISH或原代羊膜上皮细胞的侵袭。在1 μ g/ml的低浓度下，托珠单抗（抗人IL-6受体单克隆抗体）抑制IL-6诱导的MMP分泌。结论：本文首次报道了托珠单抗抑制IL-6诱导的人胎膜早破羊膜细胞分泌MMP-2和MMP-9。版权所有（C）2009 S. Karger AG，巴塞尔
Background/Aims: In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab. Methods: To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells. Results: Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10(-8) or 10(-7) M IL-6 or tumor necrosis factor (TNF)-alpha clearly increased the secretion of MMP-2 and -9. Treatment with 10(-8) M TNF-alpha or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 mu g/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion. Conclusions: This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM. Copyright (C) 2009 S. Karger AG, Basel