Skip to main content

Advertisement

Log in

Fluoride Can Damage the Spleen of Mice by Perturbing Th1/Th2 Cell Balance

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

To investigate the mechanism of fluoride-induced splenic toxicity, 0, 25, 50, and 100 mg/L sodium fluoride (NaF) were administered in male mice via drinking water for 90 days. After NaF treatment, the histological structure of the spleen, the proportion of helper T 1 cell (Th1) and helper T 2 cell (Th2), and the relative expression levels of cytokines and T-bet and GATA3 were analyzed. The results showed that 50 and 100 mg/L NaF consumption can change the normal structure of mouse spleen and the proportion of Th1/Th2 cells. It also decreased the mRNA expression levels of IL-2, INF-γ, and TGF-β, but increased the levels of IL-4, IL-6, and IL-10. Importantly, fluoride increased the protein expression of GATA3 but decreased the expression of T-bet. Our findings indicate that superfluous fluoride intake damages the balance of Th1/Th2 cells by changing the levels of T-bet and GATA3 in the spleen, and further changes the expression of Th1/Th2 cell-related cytokines in the spleen microenvironment, eventually leading to spleen injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Buzalaf MAR (2018) Review of fluoride intake and appropriateness of current guidelines. Adv Dent Res 29(2):157–166

    Article  CAS  Google Scholar 

  2. Tayibi H, Choura M, Lopez FA, Alguacil FJ, Lopez-Delgado A (2009) Environmental impact and management of phosphogypsum. J Environ Manag 90(8):2377–2386

    Article  CAS  Google Scholar 

  3. Niu R, Xue X, Zhao Y, Sun Z, Yan X, Li X, Feng C, Wang J (2015) Effects of fluoride on microtubule ultrastructure and expression of Tubalpha1a and Tubbeta2a in mouse hippocampus. Chemosphere. 139:422–427

    Article  CAS  Google Scholar 

  4. Sun Z, Nie Q, Zhang L, Niu R, Wang J, Wang S (2017) Fluoride reduced the immune privileged function of mouse Sertoli cells via the regulation of Fas/FasL system. Chemosphere. 168:318–325

    Article  CAS  Google Scholar 

  5. Wang HW, Miao CY, Liu J, Zhang Y, Zhu SQ, Zhou BH (2019) Fluoride-induced rectal barrier damage and microflora disorder in mice. Environ Sci Pollut Res Int 27(7):7596–7607

  6. Shi Z, Zhan Y, Zhao J, Wang J, Ma H (2016) Effects of fluoride on the expression of p38MAPK signaling pathway-related genes and proteins in spleen lymphocytes of mice. Biol Trace Elem Res 173(2):333–338

    Article  CAS  Google Scholar 

  7. Ma Y, Zhang K, Ren F, Wang J (2017) Developmental fluoride exposure influenced rat’s splenic development and cell cycle via disruption of the ERK signal pathway. Chemosphere. 187:173–180

    Article  CAS  Google Scholar 

  8. Kuang P, Guo H, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L (2019) Sodium fluoride impairs splenic innate immunity via inactivation of TLR2/MyD88 signaling pathway in mice. Chemosphere. 237:124437

    Article  CAS  Google Scholar 

  9. Deng H, Kuang P, Cui H, Chen L, Fang J, Zuo Z, Deng J, Wang X, Zhao L (2016) Sodium fluoride induces apoptosis in cultured splenic lymphocytes from mice. Oncotarget. 7(42):67880–67900

    Article  Google Scholar 

  10. Lv Y, Li Y, Liu N, Dong Y, Deng J (2019) Investigation into imbalance of Th1/Th2 cells in cirrhotic, hypersplenic rats. J Int Med Res:300060519889441. https://doi.org/10.1177/0300060519889441

  11. Kidd P (2003) Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8(3):223–246

    PubMed  Google Scholar 

  12. Zhang Y, Zhang Y, Gu W, Sun B (2014) TH1/TH2 cell differentiation and molecular signals. Adv Exp Med Biol 841:15–44

    Article  CAS  Google Scholar 

  13. Heo Y, Lee WT, Lawrence DA (1998) Differential effects of lead and cAMP on development and activities of Th1- and Th2-lymphocytes. Toxicol Sci 43(2):172–185

    CAS  PubMed  Google Scholar 

  14. Wang H, Zhou B, Niu R, Wang J, Zhang J, Wang J (2017) Analysis of the roles of dietary protein and calcium in fluoride-induced changes in T-lymphocyte subsets in rat. Environ Toxicol 32(5):1587–1595

    Article  CAS  Google Scholar 

  15. Yang L, Jin P, Wang X, Zhou Q, Lin X, Xi S (2018) Fluoride activates microglia, secretes inflammatory factors and influences synaptic neuron plasticity in the hippocampus of rats. Neurotoxicology. 69:108–120

    Article  CAS  Google Scholar 

  16. Liu J, Wang HW, Zhao WP, Li XT, Lin L, Zhou BH (2019) Induction of pathological changes and impaired expression of cytokines in developing female rat spleen after chronic excess fluoride exposure. Toxicol Ind Health 35(1):43–52

    Article  CAS  Google Scholar 

  17. Kreipe HH (2019) Neuroendocrine differentiation in breast cancer. Pathologe. 40(Suppl 3):325–330

    Article  CAS  Google Scholar 

  18. Onodera A, Kokubo K, Nakayama T (2018) Epigenetic and transcriptional regulation in the induction, maintenance, heterogeneity, and recall-response of effector and memory Th2 cells. Front Immunol 9:2929

    Article  CAS  Google Scholar 

  19. Hammam AA, Ezzat DA, Elwahab MH (2016) Differential expression of T-bet and GATA3 in Egyptian children with idiopathic thrombocytopenic purpura. Indian J Hematol Blood Transfus 32(4):460–467

    Article  Google Scholar 

  20. Kardan M, Rafiei A, Ghaffari J, Valadan R, Morsaljahan Z, Haj-Ghorbani ST (2019) Effect of ginger extract on expression of GATA3, T-bet and ROR-γt in peripheral blood mononuclear cells of patients with allergic asthma. Allergol Immunopathol (Madr) 47(4):378–385

    Article  CAS  Google Scholar 

  21. Chen C, Su X, Hu Z (2019) Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR-155. Exp Ther Med 18(3):1850–1862

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Pramanik S, Saha D (2017) The genetic influence in fluorosis. Environ Toxicol Pharmacol 56:157–162

    Article  CAS  Google Scholar 

  23. Li GS, Jing L, Xu H (2005) Progress of study on endemic fluorosis. Zhonghua Bing Li Xue Za Zhi 34(10):632–634

    PubMed  Google Scholar 

  24. Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 223(2):236–251

    Article  CAS  Google Scholar 

  25. Dubnika A, Manoukian MAC, Mohammadi MR, Parekh MB, Gurjarpadhye AA, Inayathullah M, Dubniks V, Lakey JRT, Rajadas J (2018) Cytokines as therapeutic agents and targets in heart disease. Cytokine Growth Factor Rev 43:54–68

    Article  CAS  Google Scholar 

  26. Wu TT, Li WM, Yao YM (2016) Interactions between autophagy and inhibitory cytokines. Int J Biol Sci 12(7):884–897

    Article  CAS  Google Scholar 

  27. Rutz S, Ouyang W (2016) Regulation of interleukin-10 expression. Adv Exp Med Biol 941:89–116

    Article  CAS  Google Scholar 

  28. Singh R, Alape D, de Lima A, Ascanio J, Majid A, Gangadharan SP (2019) Regulatory T cells in respiratory health and diseases. Pulm Med 2019:1907807

    Article  Google Scholar 

  29. Xiao K, Zou WH, Yang Z, Rehman ZU, Ansari AR, Yuan HR, Zhou Y, Cui L, Peng KM, Song H (2015) The role of visfatin on the regulation of inflammation and apoptosis in the spleen of LPS-treated rats. Cell Tissue Res 359(2):605–618

    Article  CAS  Google Scholar 

  30. Fang D, Zhu J (2017) Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets. J Exp Med 214(7):1861–1876

    Article  CAS  Google Scholar 

  31. Stadhouders R, Lubberts E, Hendriks RW (2018) A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun 87:1–15

    Article  CAS  Google Scholar 

  32. Sopel N, Graser A, Mousset S, Finotto S (2016) The transcription factor BATF modulates cytokine-mediated responses in T cells. Cytokine Growth Factor Rev 30:39–45

    Article  CAS  Google Scholar 

  33. Van Gool F, Nguyen MLT, Mumbach MR, Satpathy AT, Rosenthal WL, Giacometti S, Le DT, Liu W, Brusko TM, Anderson MS, Rudensky AY, Marson A, Chang HY, Bluestone JA (2019) A mutation in the transcription factor Foxp3 drives T helper 2 effector function in regulatory T cells. Immunity 50(2):362–377.e6

    Article  Google Scholar 

  34. Maehara T, Moriyama M, Kawano S, Hayashida JN, Furukawa S, Ohta M, Tanaka A, Yamauchi M, Ohyama Y, Kiyoshima T, Nakamura S (2015) Cytokine profiles contribute to understanding the pathogenic difference between good syndrome and oral lichen planus: two case reports and literature review. Medicine (Baltimore) 94(14):e704

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by National Natural Science Foundation of China (grant no. 31672623) and Veterinary Environmental Lab (Shanxi Key Lab).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jundong Wang.

Ethics declarations

Conflict of Interest

The authors declare that there are no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Du, X., Zhao, Y. et al. Fluoride Can Damage the Spleen of Mice by Perturbing Th1/Th2 Cell Balance. Biol Trace Elem Res 199, 1493–1500 (2021). https://doi.org/10.1007/s12011-020-02264-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02264-y

Keywords

Navigation