TCR and IL-12 receptor signals cooperate to activate an individual response element in the IFN-gamma promoter in effector Th cells
| Autor: | F, Zhang, T, Nakamura, T M, Aune |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
CD3 Complex
Immune Sera Receptors Antigen T-Cell Receptors Interleukin-12 Nuclear Proteins Mice Transgenic Receptors Interleukin T-Lymphocytes Helper-Inducer Lymphocyte Activation Response Elements Interleukin-12 Mice Inbred C57BL Interferon-gamma Mice Immune Tolerance Mice Inbred CBA Animals Mitogens Promoter Regions Genetic Cells Cultured Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(2) |
| ISSN: | 0022-1767 |
| Popis: | IFN-gamma is a key regulatory cytokine of the immune system. Reporter transgenic mice expressing the luciferase gene under the control of separate TCR-response elements (TCR-RE) from the IFN-gamma promoter or expressing the green fluorescent protein gene under the control of an IFN-gamma "minigene" were employed to explore the basis for IL-12 regulation of IFN-gamma gene transcription. In the absence of TCR stimulation, IL-12 did not activate the TCR-REs but did induce green fluorescent protein expression. TCR plus IL-12R stimulation of effector Th cells resulted in: 1) enhanced activation of the proximal, but not the distal, TCR-RE, and 2) increased induction of cJun-proximal TCR-RE complexes and c-Jun protein expression. Overexpression of cJun, but not cFos, increased activity of the proximal TCR-RE in T cells. These results suggest that IL-12R signaling affects IFN-gamma gene transcription by at least two separate mechanisms; IL-12R signaling without TCR signaling targets promoter regions outside of the approximately 100-bp IFN-gamma TCR-RE, and IL-12R signaling also stimulates TCR-induced activity of the proximal TCR-RE. |
| Databáze: | OpenAIRE |
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