Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis

Nirupama Chandel, Bipin Sharma, Divya Salhan, Mohammad Husain, Ashwani Malhotra, Shilpa J Buch, Pravin C. Singhal

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT1 receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.

Original languageEnglish (US)
Pages (from-to)C607-C615
JournalAmerican Journal of Physiology - Cell Physiology
Volume303
Issue number6
DOIs
StatePublished - Sep 15 2012

Fingerprint

Calcitriol Receptors
Renin-Angiotensin System
Morphine
Down-Regulation
Apoptosis
T-Lymphocytes
Reactive Oxygen Species
Opioid Receptors
DNA Repair
Opiate Alkaloids
Naltrexone
Losartan

Keywords

  • Apoptosis
  • Morphine
  • Renin-angiotensin system
  • T cells
  • Vitamin D receptor

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis. / Chandel, Nirupama; Sharma, Bipin; Salhan, Divya; Husain, Mohammad; Malhotra, Ashwani; Buch, Shilpa J; Singhal, Pravin C.

In: American Journal of Physiology - Cell Physiology, Vol. 303, No. 6, 15.09.2012, p. C607-C615.

Research output: Contribution to journalArticle

Chandel, Nirupama ; Sharma, Bipin ; Salhan, Divya ; Husain, Mohammad ; Malhotra, Ashwani ; Buch, Shilpa J ; Singhal, Pravin C. / Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis. In: American Journal of Physiology - Cell Physiology. 2012 ; Vol. 303, No. 6. pp. C607-C615.
@article{5147180cdbb14f4199714dd9be02d76d,
title = "Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis",
abstract = "Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT1 receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.",
keywords = "Apoptosis, Morphine, Renin-angiotensin system, T cells, Vitamin D receptor",
author = "Nirupama Chandel and Bipin Sharma and Divya Salhan and Mohammad Husain and Ashwani Malhotra and Buch, {Shilpa J} and Singhal, {Pravin C.}",
year = "2012",
month = "9",
day = "15",
doi = "10.1152/ajpcell.00076.2012",
language = "English (US)",
volume = "303",
pages = "C607--C615",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Vitamin D receptor activation and downregulation of renin-angiotensin system attenuate morphine-induced T cell apoptosis

AU - Chandel, Nirupama

AU - Sharma, Bipin

AU - Salhan, Divya

AU - Husain, Mohammad

AU - Malhotra, Ashwani

AU - Buch, Shilpa J

AU - Singhal, Pravin C.

PY - 2012/9/15

Y1 - 2012/9/15

N2 - Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT1 receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.

AB - Opiates have been reported to induce T cell loss. We evaluated the role of vitamin D receptor (VDR) and the activation of the renin-angiotensin system (RAS) in morphine-induced T cell loss. Morphine-treated human T cells displayed downregulation of VDR and the activation of the RAS. On the other hand, a VDR agonist (EB1089) enhanced T cell VDR expression both under basal and morphine-stimulated states. Since T cells with silenced VDR displayed the activation of the RAS, whereas activation of the VDR was associated with downregulation of the RAS, it appears that morphine-induced T cell RAS activation was dependent on the VDR status. Morphine enhanced reactive oxygen species (ROS) generation in a dose-dependent manner. Naltrexone (an opiate receptor antagonist) inhibited morphine-induced ROS generation and thus, suggested the role of opiate receptors in T cell ROS generation. The activation of VDR as well as blockade of ANG II (by losartan, an AT1 receptor blocker) also inhibited morphine-induced T cell ROS generation. Morphine not only induced double-strand breaks (DSBs) in T cells but also attenuated DNA repair response, whereas activation of VDR not only inhibited morphine-induced DSBs but also enhanced DNA repair. Morphine promoted T cell apoptosis; however, this effect of morphine was inhibited by blockade of opiate receptors, activation of the VDR, and blockade of the RAS. These findings indicate that morphine-induced T cell apoptosis is mediated through ROS generation in response to morphine-induced downregulation of VDR and associated activation of the RAS.

KW - Apoptosis

KW - Morphine

KW - Renin-angiotensin system

KW - T cells

KW - Vitamin D receptor

UR - http://www.scopus.com/inward/record.url?scp=84866419371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866419371&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00076.2012

DO - 10.1152/ajpcell.00076.2012

M3 - Article

C2 - 22763121

AN - SCOPUS:84866419371

VL - 303

SP - C607-C615

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 6

ER -