Int J Med Sci 2021; 18(8):1746-1752. doi:10.7150/ijms.53999 This issue

Research Paper

Acid-electrolyzed functional water-induces Interleukin-1α release from Intracellular Storage Sites in Oral Squamous Cell Carcinoma

Tomoko Takemoto1,2, Ryo Kaetsu1,2, Machiko Hanayama3, Yuuichi Ishiyama3, Masayuki Sadamura3, Kensuke Nishio4,5, Mariko Tsunoda6,7, Masatake Asano6,7✉, Mitsuru Motoyoshi1,8

1. Department of Orthodontics, Nihon University School of Dentistry, Tokyo, Japan.
2. Division of Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry, Tokyo, Japan.
3. Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, Tokyo, Japan.
4. Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan.
5. Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan, 101-8310.
6. Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan.
7. Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
8. Division of Clinical Research, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.

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Citation:
Takemoto T, Kaetsu R, Hanayama M, Ishiyama Y, Sadamura M, Nishio K, Tsunoda M, Asano M, Motoyoshi M. Acid-electrolyzed functional water-induces Interleukin-1α release from Intracellular Storage Sites in Oral Squamous Cell Carcinoma. Int J Med Sci 2021; 18(8):1746-1752. doi:10.7150/ijms.53999. Available from https://www.medsci.org/v18p1746.htm

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Abstract

Graphic abstract

The aim of this study was to examine the acid-electrolyzed functional water (FW)-mediated cytokine release in an oral squamous cell carcinoma-derived cell line (OSCC) following treatment with FW. FW is generated by the electrolysis of a sodium chloride solution and accelerate the burn wound healing. To elucidate the underlying mechanisms, the cytokine/chemokine secretion profile of HSC3 cells was examined using a cytokine array. FW treatment significantly induced interleukin (IL)-1α secretion, which was confirmed by enzyme-linked immunosorbent assay. Subsequently, the HSC3 cells were pre-treated with cycloheximide (CHX) for 1 h prior to FW stimulation to determine whether the augmented IL-1α secretion was due to enhanced protein synthesis. CHX pre-treatment did not affect IL-1α secretion suggesting that the secreted IL-1α might have been derived from intracellular storage sites. The amount of IL-1α in the cell lysate of the FW-treated HSC3 cells was significantly lower than that of the non-treated cells. Immunofluorescence staining using a polyclonal antibody against full-length IL-1α revealed a drastic reduction in IL-1α inside the FW- treated cells. IL-1α is synthesized in its precursor form (pIL-1α) and cleaved to produce pro-piece and mature IL-1α (ppIL-1α and mIL-1α) inside the cells. In the present study, only pIL-1α was detected within the HSC3 cells in its resting state. However, FW stimulation resulted in the release of the 33 kDa and two other smaller forms (about 19 kDa) of the protein. These results indicates that FW treatment induces IL-1α secretion, a typical alarmin, from the intracellular storage in OSCC cells.

Keywords: acid-electrolyzed functional water, interleukin-1α, oral squamous cell carcinoma-derived cell line, alarmin