Format

Send to

Choose Destination
FEBS Lett. 2002 Nov 6;531(2):348-53.

IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages.

Author information

1
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, Japan. amasumi@nih.go.jp

Abstract

IRF-8/ICSBP and IRF-1 are IRF family members whose expression is induced in response to IFN-gamma in macrophages. IL-12 is a cytokine produced in macrophages that plays a critical role in host defense. IFN-gamma and bacterial lipopolysaccharide (LPS) induce IL-12p40 transcription, which is necessary for the production of IL-12. We have previously shown that IL-12p40 expression is impaired in ICSBP-deficient mice and that transfection of ICSBP together with IRF-1 can activate IL-12p40 expression in mouse macrophage cells. To further study the role of ICSBP and IRF-1, we investigated murine IL-12p40 promoter activity in the macrophage cell line RAW 264.7. We show here that co-transfection of ICSBP and IRF-1 synergistically stimulates IL-12 promoter activity to a level comparable to that induced by IFN-gamma/LPS. Mutation of the Ets or NFkappaB site previously shown to be important for IL-12p40 transcription did not abolish the activation by ICSBP and IRF-1. However, mutation of the ISRE-like site found downstream from the NFkappaB and C/EBP sites abrogated the activation by ICSBP and IRF-1. Together, these results indicate that ICSBP and IRF-1 cooperatively stimulate murine IL-12 transcription through a novel regulatory element in the murine promoter.

PMID:
12417340
DOI:
10.1016/s0014-5793(02)03556-1
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center