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Int J Med Sci 2017; 14(12):1173-1180. doi:10.7150/ijms.20387 This issue Cite

Research Paper

EMMPRIN Inhibits bFGF-Induced IL-6 Secretion in an Osteoblastic Cell Line, MC3T3-E1

Akari Saiki¹, Mitsuru Motoyoshi^{1, 2}, Keiko Motozawa^{1, 3}, Teinosuke Okamura^{4, 5}, Kousuke Ueki^{3, 6}, Noriyoshi Shimizu^{1, 2}, Masatake Asano^{7, 8✉}

1. Department of Orthodontics, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
2. Division of Clinical Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
3. Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
4. Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
5. Department of Endodontics, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
6. Department of Oral and Maxillofacial Surgery, Division of Oral Surgery, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
7. Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan;
8. Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.

✉ Corresponding author: Masatake Asano, Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Phone: +81-3-3219-8114 E-mail: asano.masatakeac.jp

Abstract

Background: Electrolytically-generated acid functional water (FW) is obtained by electrolyzing low concentrations of saline. Although it has been widely used in clinical practice with various purposes, the underlying mechanisms of action involved have not been fully elucidated so far. We used the human cervical cancer-derived fibroblastic cell line (HeLa), to examine the cytokine secretion profile following FW treatment in the present study.

Results: FW stimulation significantly induced the secretion of basic fibroblast growth factor (bFGF) and extracellular matrix metalloproteinase inducer (EMMPRIN). The effect of both factors on osteoblast-like MC3T3-E1 cells was further examined by stimulating the cells with the conditioned medium of FW-stimulated HeLa cells. However, the conditioned medium failed to induce IL-6 secretion. The MC3T3-E1 cells were further stimulated with recombinant bFGF or EMMPRIN or a combination of both factors. Intriguingly, bFGF-stimulated IL-6 induction was totally inhibited by EMMPRIN. Pretreatment with the specific inhibitor of nuclear factor-kappa B (NF-κB) drastically inhibited IL-6 secretion indicating that bFGF-induced IL-6 expression was dependent on NF-κB activation. The phosphorylation status of NF-κB p65 subunit was further examined. The results indicated that EMMPRIN inhibited bFGF-induced NF-κB p65 phosphorylation.

Conclusions: These findings suggest that bFGF can induce IL-6 secretion in MC3T3-E1 cells through NF-κB activation. As EMMPRIN inhibited bFGF-induced IL-6 secretion by reducing the p65 subunit phosphorylation, it might be concluded that bFGF and EMMPRIN crosstalk in their respective signaling pathways.

Keywords: EMMPRIN, bFGF, IL-6, osteoblast.

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