Suppression of heme oxygenase-1 mRNA expression by interferon-γ in human glioblastoma cells

Kazuhiro Takahashi, Masaharu Nakayama, Kazuhisa Takeda, Hiroyoshi Fujita, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide, and iron. Heme oxygenase-1 is an inducible isozyme and is expressed in many types of cells and tissues. Large amounts of these heme degradation products may be noxious to the host, especially in the brain. We therefore searched for the factors that suppress the expression of heme oxygenase-1. Northern blot analysis showed that treatment with interferon-γ and with interleukin-1β for 24 h decreased the expression levels of heme oxygenase-1 mRNA to ~20 and ~50% of the control levels, respectively, in a human glioblastoma cell line, T98G. Treatment with a combination of these two cytokines additively decreased the expression levels of heme oxygenase-1 mRNA. Western blot analysis showed that the expression level of heme oxygenase-1 protein was also decreased by treatment with interferon-γ, but not with interleukin-1β. Moreover, pretreatment with interferon-γ partially suppressed the induction of heine oxygenase-1 mRNA expression caused by either sodium nitroprusside, cadmium, or hemin. These findings raise the possibility that the expression of heine oxygenase-1 is down-regulated by interferon-γ in the nervous system.

Original languageEnglish
Pages (from-to)2356-2361
Number of pages6
JournalJournal of Neurochemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 1999

Keywords

  • Brain
  • Cytokine
  • Glioblastoma
  • Heme oxygenase
  • Interferon
  • Interleukin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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