Heme oxygenase-1 protects regulatory T cells from hypoxia-induced cellular stress in an experimental mouse brain tumor model

Mahua Dey, Alan L. Chang, Derek A. Wainwright, Atique U. Ahmed, Yu Han, Irina V. Balyasnikova, Maciej S. Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Two characteristic features of malignant gliomas (MG) are the presence of hypoxia and accumulation of regulatory T cells (Tregs). Heme-oxygenase-1 (HO1) is a cytoprotective enzyme expressed in high level by Tregs in glioma. In this study, we show that higher HO1 expression in Tregs is associated with increased survival under hypoxic conditions and that HO1 inhibitor, tin protoporphyrin (SnPP), abrogates the survival benefits. Moreover, SnPP preferentially eliminates Tregs and treatment with SnPP of tumor bearing mice significantly increases survival (23 to 31. days (p<. 0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.

Original languageEnglish (US)
Pages (from-to)33-42
Number of pages10
JournalJournal of Neuroimmunology
Volume266
Issue number1-2
DOIs
StatePublished - Jan 15 2014

Fingerprint

Cell Hypoxia
Heme Oxygenase-1
Regulatory T-Lymphocytes
Brain Neoplasms
Glioma
Enzymes
Neoplasms

Keywords

  • Glioma
  • Heme oxygenase 1
  • Hypoxia
  • Immunization
  • Regulatory T cells
  • Tin protoporphyrin

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

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title = "Heme oxygenase-1 protects regulatory T cells from hypoxia-induced cellular stress in an experimental mouse brain tumor model",
abstract = "Two characteristic features of malignant gliomas (MG) are the presence of hypoxia and accumulation of regulatory T cells (Tregs). Heme-oxygenase-1 (HO1) is a cytoprotective enzyme expressed in high level by Tregs in glioma. In this study, we show that higher HO1 expression in Tregs is associated with increased survival under hypoxic conditions and that HO1 inhibitor, tin protoporphyrin (SnPP), abrogates the survival benefits. Moreover, SnPP preferentially eliminates Tregs and treatment with SnPP of tumor bearing mice significantly increases survival (23 to 31. days (p<. 0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.",
keywords = "Glioma, Heme oxygenase 1, Hypoxia, Immunization, Regulatory T cells, Tin protoporphyrin",
author = "Mahua Dey and Chang, {Alan L.} and Wainwright, {Derek A.} and Ahmed, {Atique U.} and Yu Han and Balyasnikova, {Irina V.} and Lesniak, {Maciej S.}",
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TY - JOUR

T1 - Heme oxygenase-1 protects regulatory T cells from hypoxia-induced cellular stress in an experimental mouse brain tumor model

AU - Dey, Mahua

AU - Chang, Alan L.

AU - Wainwright, Derek A.

AU - Ahmed, Atique U.

AU - Han, Yu

AU - Balyasnikova, Irina V.

AU - Lesniak, Maciej S.

PY - 2014/1/15

Y1 - 2014/1/15

N2 - Two characteristic features of malignant gliomas (MG) are the presence of hypoxia and accumulation of regulatory T cells (Tregs). Heme-oxygenase-1 (HO1) is a cytoprotective enzyme expressed in high level by Tregs in glioma. In this study, we show that higher HO1 expression in Tregs is associated with increased survival under hypoxic conditions and that HO1 inhibitor, tin protoporphyrin (SnPP), abrogates the survival benefits. Moreover, SnPP preferentially eliminates Tregs and treatment with SnPP of tumor bearing mice significantly increases survival (23 to 31. days (p<. 0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.

AB - Two characteristic features of malignant gliomas (MG) are the presence of hypoxia and accumulation of regulatory T cells (Tregs). Heme-oxygenase-1 (HO1) is a cytoprotective enzyme expressed in high level by Tregs in glioma. In this study, we show that higher HO1 expression in Tregs is associated with increased survival under hypoxic conditions and that HO1 inhibitor, tin protoporphyrin (SnPP), abrogates the survival benefits. Moreover, SnPP preferentially eliminates Tregs and treatment with SnPP of tumor bearing mice significantly increases survival (23 to 31. days (p<. 0.05)). Thus HO1 inhibition provides another alternative way of therapeutically targeting Tregs in MG.

KW - Glioma

KW - Heme oxygenase 1

KW - Hypoxia

KW - Immunization

KW - Regulatory T cells

KW - Tin protoporphyrin

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JF - Journal of Neuroimmunology

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