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

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.

Toxicity of Terahertz-Based Functional Mineral Water (Plant-Derived) to Immature Stages of Mosquito Vectors

“…Recently, functional water has been used in many agricultural and medicinal applications [ 10 , 11 , 12 ]. In the present study, our findings indicated that terahertz-based functional mineral water was also toxic to the larvae and pupae of the three tested mosquito species in a concentration-dependent manner (0–333 ppm).…”

“…For example, guppies ( Poecilia reticulata ) are frequently introduced to both natural and artificial water bodies as biological control agents for mosquitoes [ 8 , 9 ]. Another example is functional water produced from plant-derived minerals, or acid electrolyzed water, which has proven useful in agricultural pest control and medicinal disinfection [ 10 , 11 , 12 , 13 ].…”

Bone regeneration is enhanced by the combined use of acid‐electrolyzed functional water with hydroxyapatite/collagen composite

“…To explore the factors deeply involved in these effects, we generated a FW with several different characters in ongoing experiments, yet, no obvious factors have been identified so far. FW‐treated cells were found to release lactate dehydrogenase (LDH) into the culture media (Kusunoki et al, ). LDH is a cell damage marker, and the FW‐treated cells were expected to be damaged to some extent.…”

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

“…Although the underlying mechanisms have not been elucidated, these beneficial effects of FW might be attributed to increased cytokine release. Previously, we demonstrated that the treatment of several cell lines with FW resulted in the release of various factors 5 , 6 , 7 . Among them, the release of extracellular matrix metalloproteinase inducer (EMMPRIN) was significantly augmented in the human oral squamous cell carcinoma cell line (OSCC) HSC3 7 .…”

“…Previously, we demonstrated that the treatment of several cell lines with FW resulted in the release of various factors 5 , 6 , 7 . Among them, the release of extracellular matrix metalloproteinase inducer (EMMPRIN) was significantly augmented in the human oral squamous cell carcinoma cell line (OSCC) HSC3 7 . Augmented EMMPRIN secretion was not regulated at the transcriptional level and appeared to be released from intracellular storage sites.…”