Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells

  • Authors:
    • Hui-Wei Huang
    • Cong Zuo
    • Xiao Chen
    • Yu-Ping Peng
    • Yi-Hua Qiu
  • View Affiliations

  • Published online on: June 14, 2016     https://doi.org/10.3892/ijmm.2016.2639
  • Pages: 635-642
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Abstract

The aim of the present study was to examine the effect of the overexpression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines (CAs), in lymphocytes on the differentiation and function of T helper (Th) cells. A recombinant TH overexpression plasmid (pEGFP-N1-TH) was constructed and transfected into mesenteric lymphocytes using nucleofection technology. These cells were stimulated with concanavalin A (Con A) for 48 h and then examined for TH expression and CA content, as well as for the percentage of Th1 and Th2 cells, cytokine concentrations and for the levels of signaling molecules. The lymphocytes overexpressing TH also expressed higher mRNA and protein levels of TH, and synthesized more CAs, including norepinephrine (NE), epinephrine (E) and dopamine (DA) than the mock-transfected control cells. TH gene overexpression in the lymphocytes reduced the percentage of interferon-γ (IFN-γ)-producing CD4+ cells and the ratio of CD4+IFN-γ+/CD4+IL-4+ cells, as well as the percentages of CD4+CD26+ and CD4+CD30+ cells and the ratio of CD4+CD26+/CD4+CD30+ cells. TH overexpression also reduced the secretion of IFN-γ and tumor necrosis factor (TNF) from lymphocytes. Moreover, NE inhibited the Con A-induced lymphocyte proliferation and decreased both cyclic adenosine monophosphate (cAMP) levels and p38 mitogen-activated protein kinase (MAPK) expression in the lymphocytes. Our findings thus indicate that TH gene overexpression promotes the polarization and differentiation of CD4+ cells towards Th2 cells, and this effect is mediated by the cAMP and p38 MAPK signaling pathways.
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August-2016
Volume 38 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huang H, Zuo C, Chen X, Peng Y and Qiu Y: Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells. Int J Mol Med 38: 635-642, 2016.
APA
Huang, H., Zuo, C., Chen, X., Peng, Y., & Qiu, Y. (2016). Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells. International Journal of Molecular Medicine, 38, 635-642. https://doi.org/10.3892/ijmm.2016.2639
MLA
Huang, H., Zuo, C., Chen, X., Peng, Y., Qiu, Y."Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells". International Journal of Molecular Medicine 38.2 (2016): 635-642.
Chicago
Huang, H., Zuo, C., Chen, X., Peng, Y., Qiu, Y."Effect of tyrosine hydroxylase overexpression in lymphocytes on the differentiation and function of T helper cells". International Journal of Molecular Medicine 38, no. 2 (2016): 635-642. https://doi.org/10.3892/ijmm.2016.2639