Pro-inflammatory Cytokines Are Involved in Fluoride-Induced Cytotoxic Potential in HeLa Cells

Abstract

This study was designed to investigate the pro-inflammatory cytokines and their involvement in the cytotoxic potential of fluoride (F) in HeLa cells. HeLa cells were cultured with varying F concentrations (1-50 mg/L) for 48 h, and treatment effects were analyzed. The viability of HeLa cells was determined with a colorimetric method. The concentrations of IL-1β, IL-2, IL-6, and TNF-a in culture supernatant were measured through enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of IL-1β, IL-2, IL-6 and TNF-a were subjected to transcript analysis and quantified through reverse transcription real-time PCR. Results showed that 10, 20 and 50 mg/L F significantly decreased the viability of HeLa cells incubated for 24 and 48 h. With their cytotoxic effect, the concentrations of IL-1β, IL-2, IL-6, and TNF-a decreased significantly in response to F, especially at 20 and 50 mg/L for 48 h. The mRNA expression levels of IL-1β, IL-2, IL-6, and TNF-a were downregulated at 50 mg/L F for 48 h. Therefore, F inhibited HeLa cell growth; as such, F could be used to alleviate the inhibition of pro-inflammatory cytokine expression.

Comparative Transcriptomics Reveals the Role of the Toll-Like Receptor Signaling Pathway in Fluoride-Induced Cardiotoxicity

“…It has been reported that NaF can suppress the cellular immunity in mice and Th2 cytokines, including IL-4, IL-6, and IL-10, and Th17 cytokine (IL-17A) contents were decreased after exposed to NaF in excess of 12 mg/kg . In addition, our findings are consistent with some reports that high fluoride decreased the percentages of thymic CD4+ and CD8+T cells and IL-2 and IL-10 mRNA expression in mice, and at the cellular level, high NaF concentrations (20 and 50 mg/L) significantly reduced the secretion of TNF-α, IL-2, IL-6, and IL-1β in the supernatant . Therefore, we speculate that NaF affects the inflammation and immune response of rat heart tissue by affecting factors such as IL-6 and IL-10.…”

“…Elevated IL-6 level is related to cardiac hypertrophy, heart failure, and cardiac fibrosis . Related work indicates that NaF could down-regulate the levels of cytokines such as IL-2, IL-4, IL-6, IL-10, and TNF-α. − After tissue damage, IL-6 and IL-1 can be rapidly produced to stimulate acute phase reactions, hematopoiesis, and immune responses, which contribute to host defenses, but continuous up-regulation can lead to pathological changes in chronic inflammation and autoimmunity. As an anti-inflammatory cytokine, IL-10 plays a protective role in the heart .…”

Sodium fluoride induces renal inflammatory responses by activating NF-κB signaling pathway and reducing anti-inflammatory cytokine expression in mice

“…Exposure to fluoride has been shown to induce inflammatory responses in lung epithelial cells [ 39 ], HeLa cells [ 40 ], THP1 differentiated monocytes/macrophages [ 32 ], peritoneal macrophages [ 36 ], aorta [ 16 ], neuron [ 37 ] and testicle [ 20 , 21 ]. However, very limited reports are focused on fluoride-induced inflammatory responses in vivo .…”

Potential Role of Fluoride in the Etiopathogenesis of Alzheimer’s Disease

“…An in vitro study by Wang et al on HeLa cells showed a fluoride-induced stimulation of the synthesis of proinflammatory cytokines IL-1β, IL-2, IL-6, and TNF-α [87]. Activation of microglia in the hippocampus and cerebral cortex was also demonstrated in the rat model where fluoride, by influencing the production of these cytokines, contributed to the formation and progression of inflammation in the brain [88].…”