International Journal of Medical Sciences

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21 November 2018

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Int J Med Sci 2018; 15(12):1365-1372. doi:10.7150/ijms.26186

Research Paper

Acid-electrolyzed functional water induces extracellular matrix metalloproteinase inducer, a possible novel alarmin, secretion from oral squamous cell carcinoma cell lines

Masafumi Kusunoki1, Eri Sata2,3, Kensuke Nishio4, Takayoshi Tanaka5,6, Tetsuya Nishida1,7, Naoyuki Sugano1,7, Shuichi Sato1,7, Masatake Asano8,9,✉

1. Department of Periodontology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan
2. Department of Orthodontics, 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. Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan
5. Maxillofacial Prosthetic Clinic, Nihon University School of Dentistry, Tokyo, Japan
6. Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan
7. Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan
8. Department of Pathology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan
9. Division of Immunology and Pathobiology, Nihon University School of Dentistry, 1-8-13 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) secretion was induced in the oral squamous cell carcinoma cell line HSC3 cell by acid-electrolyzed functional water (FW) stimulation. Augmented EMMPRIN secretion was not under transcriptional control; rather, it was derived from the intracellular storages. EMMPRIN secretion was also induced under oxidative stress and accompanied by the release of lactate dehydrogenase (LDH). The molecules released from cells undergoing necrosis are called as alarmins, and the secretion of IL-1α, a typical alarmin, was induced by FW stimulation and oxidative stress. Intracellular localization was examined by cell fractionation. A significant amount of EMMPRIN was localized in the triton X-100 and DNase sensitive fractions; the levels were drastically reduced following FW treatment. The function of the released EMMPRIN was examined using the monocytic cell line THP1. Culture supernatant derived from FW-treated HSC3 cells induced the expression of matrix metalloproteinases (MMPs) 1, 2, 8, 9, 13, and 14, platelet-derived growth factor, and interleukin-8. In contrast, vascular endothelial growth factor expression was reduced. Induction of these factors was abolished following eliminating of EMMPRIN by immunoprecipitation. These results indicate that EMMPRIN might be considered as a type of alarmin that transduces danger signals to the surrounding cells.

Keywords: Acid-electrolyzed functional water, Extracellular matrix metalloproteinase inducer, Oral squamous cell carcinoma, Matrix metalloproteinase

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How to cite this article:
Kusunoki M, Sata E, Nishio K, Tanaka T, Nishida T, Sugano N, Sato S, Asano M. Acid-electrolyzed functional water induces extracellular matrix metalloproteinase inducer, a possible novel alarmin, secretion from oral squamous cell carcinoma cell lines. Int J Med Sci 2018; 15(12):1365-1372. doi:10.7150/ijms.26186. Available from http://www.medsci.org/v15p1365.htm