title: 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.
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Kuang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Hengmin
authors.initials: H
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Deng
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya'an 625014, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival; D020128:Inhibitory Concentration 50; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012969:Sodium Fluoride / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; C000604812:CD19 antigen, mouse; D017252:CD3 Complex; C556062:IL10 protein, mouse; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D012969:Sodium Fluoride
keywords: cell cycle; cytokine; sodium fluoride; splenic B lymphocytes; splenic T lymphocytes