Enhanced B7-2 gene expression by interferon-γ in human monocytic cells is controlled through transcriptional and posttranscriptional mechanisms

R. E. Curiel, C. S. Garcia, S. Rottschafer, M. C. Bosco, I. Espinoza-Delgado

Research output: Contribution to journalArticle

Abstract

B7-2 is a costimulatory molecule expressed on professional antigen- presenting cells that provides T cells with a critical signal resulting in T- cell activation. Interferon-γ (IFN-γ) enhances B7-2 protein expression in monocytic cells. However, the molecular mechanisms controlling the enhanced expression of B7-2 are poorly understood. Northern blot and flow cytometry analysis revealed that human monocytes and the human monocytic cell line MonoMac6 (MM6) constitutively expressed B7-2 mRNA and protein and IFN-γ treatment further enhanced the expression of both molecules. The ability of IFN-γ to enhance B7-2 mRNA was evident at the dose of 31 U/mL and reached plateau levels at 500 U/mg. The effects of IFN-γ on B7-2 mRNA expression were time dependent and occurred within 3 hours of treatment and increased through 24 hours. In vitro transcription assays and mRNA stability experiments showed that IFN-γ increases both transcriptional activity and the stability of B7-2 mRNA. Treatment of MM6 cells with cycloheximide showed that de novo protein synthesis was not required for the IFN-γ-enhanced expression of B7-2 mRNA. Overall, these studies show for the first time that IFN-γ-enhanced expression of B7-2 protein in human monocytic cells is controlled at the gene level through a dual mechanism involving transcriptional and posttranscriptional mechanisms.

Original languageEnglish
Pages (from-to)1782-1789
Number of pages8
JournalBlood
Volume94
Issue number5
Publication statusPublished - Sep 1 1999

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ASJC Scopus subject areas

  • Hematology

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