Skip to main content

Advertisement

Log in

Up-regulation of Slc39A2(Zip2) mRNA in peripheral blood mononuclear cells from patients with pulmonary tuberculosis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Zinc is the most common trace mineral after iron in the human body. In organisms, zinc transporters help zinc influx and efflux from cells. A previous study has reported that Zip2 was up-regulated over 27-fold in human monocytic THP-1 cells, when intracellular zinc was depleted by TPEN. Our study found Zip2 was over-expressed in leukocytes of asthmatic infants, especially those in which the serum zinc level was lower than those in healthy infants. Pulmonary tuberculosis (PTB) patients have significantly low serum zinc levels. Here we investigated whether Zip2 level was changed in the patients with PTB. Zip2 mRNA and protein levels in peripheral blood mononuclear cells (PBMC) from PTB (n 1 = 23) and healthy controls (n 2 = 42) were detected by quantitative real-time PCR and western blot, respectively. mRNA expression levels of another four zinc transporters, Zip1, Zip6, Zip8 and ZnT1, were detected by quantitative real-time PCR. Zip2 mRNA level was significantly up-regulated in PTB patients (P = 0.001), and Zip8 mRNA level was significantly down-regulated compared with control individuals (P < 0.001). In contrast, there were no significant changes in mRNA levels of Zip1, Zip6 and ZnT1 in either group (P > 0.05). Zip2 protein expression levels increased in PTB patients compared with control individuals. Our study found that knockdown of ZIP2 with siRNA caused a decrease in Zip2 levels in PBMC of PTB patients, while reducing the expression of INF-γ (P < 0.01) and increasing the expression of IL-6(P < 0.01). These data provide evidence that increased expression of Zip2 gene is closely associated with immunity of PTB patients, suggesting that the Zip2 gene may play a key role in the initial infection control of the human body, by promoting and maintaining the immune response of adaptive T cells.

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

Similar content being viewed by others

References:

  1. Plum LM, Rink L, Haase H (2010) The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 7:1342–1365

    Article  PubMed  CAS  Google Scholar 

  2. Kambe T, Yamaguchi-lwai Y, Sasaki R, Nagao M (2004) Overview of mammalian zinc transporters. Cell Mol Life Sci 61:49–68

    Article  PubMed  CAS  Google Scholar 

  3. Shankar AH, Prasad AS (1998) Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68:447S–463S

    PubMed  CAS  Google Scholar 

  4. Wellinghausen N, Kirchner H, Rink L (1997) The immunobiology of zinc. Immunol Today 18:519–521

    Article  PubMed  CAS  Google Scholar 

  5. Hambidge KM, Walravens PA, Neldner KH (1977) The role of zinc in the pathogenesis and treatment of acrodermatitis enteropathica. Prog Clin Biol Res 14:329–342

    PubMed  CAS  Google Scholar 

  6. Allen JI, Perri RT, McClain CJ, Kay NE (1983) Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. J Lab Clin Med 102:577–589

    PubMed  CAS  Google Scholar 

  7. Wirth JJ, Fraker PJ, Kierszenbaum F (1989) Zinc requirement for macrophage function: effect of zinc deficiency on uptake and killing of a protozoan parasite. Immunology 68:114–119

    PubMed  CAS  Google Scholar 

  8. Fraker PJ, Jardieu P, Cook J (1987) Zinc deficiency and immune function. Arch Dermatol 123:1699–1701

    Article  PubMed  CAS  Google Scholar 

  9. Wellinghausen N (2001) Immunobiology of gestational zinc deficiency. Br J Nutr 85:S81–S86

    Article  PubMed  CAS  Google Scholar 

  10. Küry S, Dréno B, Bézieau S, Giraudet S, Kharfi M et al (2002) Identification of SLC39A4, a gene involved in acrodernatitis enteropathica. Nat Genet 31:239–240

    Article  PubMed  Google Scholar 

  11. Ramakrishnan K, Shenbagarathai R, Kavitha K, Uma A, Balasubramaniam R et al (2008) Serum zinc and albumin levels in pulmonary tuberculosis patients with and without HIV. Jpn J Infect Dis 61:202–204

    PubMed  CAS  Google Scholar 

  12. Ghulam H, Kadri SM, Manzoor A, Waseem Q, Aatif MS et al (2009) Status of zinc in pulmonary tuberculosis. J Infect Dev Ctries 3:365–368

    PubMed  CAS  Google Scholar 

  13. Xu TF, Wang XL, Yang JZ, Hu XY, Wu WF et al (2009) Overexpression of Zip-2 mRNA in the leukocytes of asthmatic infants. Pediatr Pulmonol 44:763–767

    Article  PubMed  Google Scholar 

  14. Guo L, Hu X, Xu T, Qi X, Wan Y, Liu X, Jiang Y, Zhang L (2011) Over-expression of Zip-13 mRNA in kidney and lung during dietary zinc deficiency in Wistar rats. Mol Biol Rep 38:1869–1874

    Article  PubMed  CAS  Google Scholar 

  15. Devirgiliis C, Zalewski PD, Perozzi G, Murgia C (2007) Zinc fluxes and zinc transporter genes in chronic diseases. Mutat Res 622:84–93

    Article  PubMed  CAS  Google Scholar 

  16. Cousins RJ, Blanchard RK, Popp MP, Popp MP, Liu L, Cao J et al (2003) A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells. Proc Natl Acad Sci USA 100:6952–6957

    Article  PubMed  CAS  Google Scholar 

  17. Peters JL, Dufner-Beattie J, Xu W, Geiser J, Lahner B, Salt DE et al (2007) Targeting of the mouse Slc39a2 (Zip2) gene reveals highly cell-specific patterns of expression, and unique functions in zinc, iron, and calcium homeostasis. Genesis 45:339–352

    Article  PubMed  CAS  Google Scholar 

  18. Hogstrand C, Kilie P, Nicholson RI, Taylor KM (2009) Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine. Trends Mol Med 15(3):101–111

    Article  PubMed  CAS  Google Scholar 

  19. Taylor KM, Morgan HE, Smart K, Zahari NM, Pumford S et al (2007) The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Mol Med 13:396–406

    Article  PubMed  CAS  Google Scholar 

  20. Liuzzi JP, Cousins RJ (2004) Mammalian zinc transporters. Annu Rev Nutr 24:151–172

    Article  PubMed  CAS  Google Scholar 

  21. Lioumi M, Ferguson CA, Sharpe PT, Freeman T, Marenholz I et al (1999) Isolation and characterization of human and mouse ZIRTL, a member of the IRT1 family of transporters, mapping within the epidermal differentiation complex. Genomics 62:272–280

    Article  PubMed  CAS  Google Scholar 

  22. Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281:24085–24089

    Article  PubMed  CAS  Google Scholar 

  23. Gaither LA, Eide DJ (2001) The human Z IP1 transporter mediates zinc uptake in human K 562 erythroleukemia cells. J Biol Chem 276:22258–22264

    Article  PubMed  CAS  Google Scholar 

  24. Jenkitkasemwong S, Wang CY, Mackenzie B et al (2012) Physiologic implications of metal-ion transport by ZIP14 and Zip8. Biometals 25(4):643–655

    Article  PubMed  CAS  Google Scholar 

  25. Wang CY, Jenkitkasemwong S, Duarte S, Sparkman BK et al (2012) ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. J Biol Chem 287(41):34032–34043

    Article  PubMed  CAS  Google Scholar 

  26. Bao B, Prasad AS, Beck FW, Godmere M (2003) Zinc modulates mRNA levels of cytokines. Am J Physiol Endocrinol Metab 285:E1095–E1102

    PubMed  CAS  Google Scholar 

  27. Dubaniewicz A, Trzonkowski P, Dubaniewicz-Wybieralska M et al (2007) Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: comparison of sarcoidosis with tuberculosis and healthy controls. Respirology 12(3):346–354

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from the Shandong Provincial Nature Science Foundation of China (No. ZR2011HM049).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lian-ying Zhang.

Additional information

Yan-ting Tao and Qing Huang contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tao, Yt., Huang, Q., Jiang, Yl. et al. Up-regulation of Slc39A2(Zip2) mRNA in peripheral blood mononuclear cells from patients with pulmonary tuberculosis. Mol Biol Rep 40, 4979–4984 (2013). https://doi.org/10.1007/s11033-013-2598-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-013-2598-z

Keywords

Navigation