Enhanced B7-2 Gene Expression by Interferon-γ in Human Monocytic Cells Is Controlled Through Transcriptional and Posttranscriptional Mechanisms

• Published in: Blood Vol. 94; no. 5; pp. 1782 - 1789
• Main Authors: Curiel, R.E., Garcia, C.S., Rottschafer, S., Bosco, M.C., Espinoza-Delgado, I.
• Format: Journal Article
• Language: English
• Published: 01.09.1999
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V94.5.1782.417a04_1782_1789

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/mL. 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.