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IL-1 and its receptor are translocated to the nucleus
B M Curtis1, M B Widmer, P deRoos
1Department of Protein Chemistry, Immunex Corporation, Seattle, WA 98101.
Journal of Immunology (Baltimore, Md. : 1950)
|February 15, 1990
Summary
Interleukin-1 (IL-1) and its receptor (IL-1R) move into T cells and accumulate in the nucleus. This suggests a novel nuclear signaling pathway for IL-1R in immune cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-1 (IL-1) is a key cytokine in immune responses.
- The IL-1 receptor (IL-1R) mediates IL-1 signaling at the cell surface.
- Intracellular trafficking of cytokine-receptor complexes is not fully understood.
Purpose of the Study:
- To investigate the internalization and intracellular transport of IL-1 and IL-1R in T cells.
- To determine the destination and fate of internalized IL-1 and IL-1R.
- To explore the potential for nuclear signaling by the IL-1R complex.
Main Methods:
- Utilized the murine T cell line EL-4.
- Employed radiolabeled IL-1 (125I-IL-1 alpha) to track internalization.
- Used electron microscope autoradiography to visualize intracellular localization.
- Analyzed IL-1R presence in purified nuclei.
Main Results:
- Internalized IL-1 remained bound to its receptor without degradation for up to 4 hours.
- Electron microscopy revealed accumulation of internalized IL-1 within purified nuclei.
- IL-1 extracted from nuclei was still complexed with its receptor.
- IL-1R internalization correlated with IL-1 signal transduction and growth factor production.
Conclusions:
- IL-1 binding induces the translocation of the cell surface IL-1R complex to the nucleus.
- The nucleus may serve as a site for IL-1R signaling.
- This finding suggests a novel intracellular mechanism for IL-1 action.