Suppressive effects of sodium fluoride on cultured splenic lymphocyte proliferation in mice

Abstract

Fluoride-induced immunotoxicity has been documented in vivo, but limited reports have focused on the effects of fluoride on lymphocytes in vitro. Therefore, we have examined the suppressive effects of sodium fluoride on cultured splenic lymphocytes in mice. CD3+ T lymphocytes, CD19+ B lymphocytes, cytokines, and cell-cycle markers were analyzed through the use of a cell-counting kit, western blot, and flow cytometery. Splenic lymphocytes were isolated from 3-week-old male ICR mice and exposed to sodium fluoride (0, 100, 500, and 1000 μmol/L) for 24 h. The percentages of CD3+, CD3+CD4+, CD3+CD8+ T lymphocytes and CD19+ B lymphocytes were decreased (P<0.05 or P<0.01) in the sodium fluoride-exposed cells. This finding was correlated with the alterations in expression levels of cytokine proteins and with evidence of cell-cycle arrest. Thus, protein expression levels of IL-2, TNF-α, IFN-γ, TGF-β were decreased (P<0.05 or P<0.01), and IL-10 protein expression levels were increased (P<0.05 or P<0.01). The percentage of lymphocyte in G1 phase was significantly increased (P<0.05 or P<0.01), while expression levels of cyclin E/D and CDK2/4 were markedly decreased (P<0.05 or P<0.01). These findings demonstrate that sodium fluoride exposure suppresses splenic lymphocyte proliferation, which is represented by reducing populations and activation of splenic T and B lymphocytes. Alterations of cytokine protein expression and cell cycle arrest are the molecular basis of the sodium fluoride-suppressed splenic lymphocyte proliferation, while reduction of T lymphocytes and B lymphocytes is the explanation of sodium fluoride-decreased splenic immune function in vitro.

Effects of sodium fluoride on blood cellular and humoral immunity in mice

“…We also measured the Th17 and found that IL-17A content was decreased after exposure to NaF. In our previous study, we found that high fluoride levels can reduce IL-2, IL-4, IL-6, TNF-α and IFN-γ in the cecal tonsil, and intestines of broiler chickens [ 14 ], and that NaF can reduce the percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T lymphocytes and CD19 + B lymphocytes and of IL-2, TNF-α, IFN-γ, TGF-β expression levels in cultured splenic lymphocytes of mice [ 36 ]. Our findings are consistent with the report of Yin et al [ 43 ] that high fluoride decreased the percentages of thymic CD4 + , CD8 + T cells and IL-2, IL-10 mRNA expression in mice.…”

Vitamin E and lycopene reduce coal burning fluorosis-induced spermatogenic cell apoptosis via oxidative stress-mediated JNK and ERK signaling pathways

“…Cell apoptosis is one early sign of genotoxic damage in mature testis, and plays critical roles in spermatozoa. Fluoride harbors various cellular effects and excessive fluoride may cause oxidative stress, inhibit protein secretion and transport [ 7 , 8 ], induce inflammatory response [ 9 , 10 ], and interfere with cell proliferation and migration which could be fluoride concentration and/or cell type dependent [ 8 , 11 , 12 ]. However, the underlying mechanisms of these cellular functions are less clear.…”

Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride

“…It has been demonstrated that excessive ingestion of fluoride can results in structural and functional changes in teeth and bones, such as mottling of teeth or skeletal fluorosis [ 6 – 9 ]. And along with teeth or skeletal fluorosis, pathological changes have also been reported in soft tissues including thyroid [ 10 ], thymus [ 11 ], brain [ 12 , 13 ], heart [ 14 , 15 ], liver [ 16 – 18 ], spleen [ 19 – 22 ], gastro-intestinal tract [ 23 , 24 ], cecal tonsil [ 25 , 26 ], bursa of Fabricius [ 27 ] and reproductive organs [ 28 ]. As the primary organ concerned with excretion and retention of fluoride, kidney is quite sensitive to the toxicity of fluoride [ 29 ].…”