Tocilizumab inhibits interleukin-6-mediated matrix metalloproteinase-2 and -9 secretions from human amnion cells in preterm premature rupture of membranes

Yukio Mano, Kiyosumi Shibata, Seiji Sumigama, Hiromi Hayakawa, Kazuhiko Ino, Eiko Yamamoto, Hiroaki Kajiyama, Akihiro Nawa, Fumitaka Kikkawa

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14 Citations (Scopus)

Abstract

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 10-7M IL-6 or tumor necrosis factor (TNF)-α clearly increased the secretion of MMP-2 and -9. Treatment with 10-8M TNF-α 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 μg/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.

Original languageEnglish
Pages (from-to)145-153
Number of pages9
JournalGynecologic and Obstetric Investigation
Volume68
Issue number3
DOIs
Publication statusPublished - 10-2009

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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