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

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.

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

“…To date, the biological effects of FW have been investigated using cell culture. In HeLa cells, FW stimulation induced the secretion of bFGF into the culture media (Saiki et al, ). The secreted bFGF has been shown to augment the expression of VEGF in fibroblasts (Yanagita et al, ).…”

“…The induction of these genes might be due to the effect of bFGF. In fact, stimulation of murine osteoblastic cell, MC3T3‐E1 cells, with recombinant FGF induced the secretion of VEGF (Saiki et al, ).…”

“…Electrolytically generated acid functional water (FW) is obtained by electrolyzing low concentrations of saline, and is widely used as a disinfectant in clinical practice (Cheng et al, ; Kubota et al, ; Nakae & Inaba, ). In a previous report, we demonstrated the induction of fibroblast growth factor‐2 (FGF‐2) secretion by FW in the human fibroblastic cell line HeLa (Saiki et al, ). Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine with a variety of functions (Bikfalvi, Klein, Pintucci, & Rifkin, ), and is expressed during all stages of fracture repair (Bolander, ), therefore, we speculated that FW might contribute to bone augmentation.…”

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

“…Electrolytically-generated acid functional water (FW), obtained by electrolyzing low concentrations of saline, is widely used as a disinfectant, in clinical practice 9 . In a previous report, FW was demonstrated to augment basic fibroblast growth factor (bFGF) secretion in HeLa cells 10 . As FW-treatment significantly induced the secretion of lactate dehydrogenase (LDH), a marker of cell damage, it was expected to cause some amount of damage to the cells.…”

Functional comparison of high and low molecular weight basic fibroblast growth factors

“…Acid‐electrolyzed functional water (FW) is obtained by the electrolysis of sodium chloride solution, and is widely used as a disinfectant in clinical practice . In an attempt to elucidate the biological effects of FW, the human fibroblast cell line HeLa was treated with FW and cytokine secretion profiles were examined . The results indicated that FW significantly induced bFGF secretion.…”