Interleukin-12 induces expression of interferon regulatory factor-1 via signal transducer and activator of transcription-4 in human T helper type 1 cells.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Interleukin-12 induces expression of interferon regulatory factor-1 via signal transducer and activator of transcription-4 in human T helper type 1 cells.

J Biol Chem. 1999 Mar 5;274(10):6698-703. Unique Identifier : AIDSLINE MED/99156957
Coccia EM; Passini N; Battistini A; Pini C; Sinigaglia F; Rogge L; Laboratory of Immunology, Istituto Superiore di Sanita, I-00161; Rome, Italy.

Abstract: IRF-1-deficient mice show a striking defect in the development of T helper 1 (Th1) cells. In the present report, we investigate the expression of IRF-1 during differentiation of human T helper cells. No significant differences of IRF-1 mRNA expression were found in established Th1 and Th2 cells; however, interleukin 12 (IL-12) induced a strong up-regulation of IRF-1 transcripts in Th1 but not in Th2 cells. We demonstrate that IL-12-induced up-regulation of IRF-1 is mediated by signal transducer and activator of transcription-4, which binds to the interferon (IFN)-gamma-activated sequence present in the promoter of the IRF-1 gene. Strong IL-12-dependent activation of a reporter gene construct containing the IRF-1 IFN-gamma-activated sequence element provides further evidence for the key role of signal transducer and activator of transcription-4 in the IL-12-induced up-regulation of IRF-1 transcripts in T cells. IRF-1 expression was strongly induced after stimulation of naive CD4(+) T cells via the T cell receptor, irrespective of the cytokines present at priming, indicating that this transcription factor does not play a major role in initiating a Th1-specific transcriptional cascade in differentiating helper T cells. However, our finding that IRF-1 is a target gene of IL-12 suggests that some of the IL-12-induced effector functions of Th1 cells may be mediated by IRF-1.

Keywords: JOURNAL ARTICLE Animal Cell Line DNA-Binding Proteins/*BIOSYNTHESIS/IMMUNOLOGY Human Interleukin-12/*PHARMACOLOGY Lymphocyte Transformation/DRUG EFFECTS Mice Phosphoproteins/*BIOSYNTHESIS/IMMUNOLOGY *Signal Transduction/DRUG EFFECTS/IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/IMMUNOLOGY/*METABOLISM Trans-Activation (Genetics)/IMMUNOLOGY Transcription Factors/IMMUNOLOGY/*METABOLISM
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A9960924

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