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Ethanol and Vitamin D Receptor in T Cell Apoptosis

Abstract

Ethanol has been demonstrated to cause T cell apoptosis. In the present study, we evaluated the role of VDR and the renin angiotensin system (RAS) in oxidative stress-induced T cell apoptosis. Ethanol-treated human T cells displayed down regulation of vitamin D receptor (VDR) and the activation of the RAS in the form of enhanced T cell renin expression and angiotensin II (Ang II) production. The silencing of VDR with siRNA displayed the activation of the RAS, and activation of the VDR resulted in the down regulation of the RAS. It suggested that ethanol-induced T cell RAS activation was dependent on the VDR status. T cell ROS generation by ethanol was found to be dose dependent. Conversely, ethanol-induced ROS generation was inhibited if VDR was activated or Ang II was blocked by an angiotensin II type 1 (AT1) receptor blocker (Losartan). Furthermore, it was observed that ethanol not only induced double strand breaks in T cells but also attenuated DNA repair response, whereas, VDR activation inhibited ethanol-induced double strand breaks and also enhanced DNA repairs. Since free radical scavengers inhibited ethanol-induced DNA damage, it would indicate that ethanol-induced DNA damage was mediated through ROS generation. These findings indicated that ethanol-induced T cell apoptosis was mediated through ROS generation in response to ethanol-induced down regulation of VDR and associated activation of the RAS.

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Acknowledgments

We thank the AIDS Reagents Program for providing Jurkat cells. This work was supported by grants RO1DK084910 and RO1 DK083931 (PCS) from National Institutes of Health, Bethesda, MD.

Conflict of Interest

The authors declare they have no conflict of interest.

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Correspondence to Pravin C. Singhal.

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Rehman, S., Chandel, N., Salhan, D. et al. Ethanol and Vitamin D Receptor in T Cell Apoptosis. J Neuroimmune Pharmacol 8, 251–261 (2013). https://doi.org/10.1007/s11481-012-9393-9

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Keywords

  • T cells, vitamin D receptor
  • Active vitamin D
  • Renin
  • Angiotensin II
  • Reactive oxygen species
  • AT1 receptor blocker
  • Losartan
  • Tempol
  • Catalase
  • Apoptosis
  • DNA damage
  • DNA repair