The interleukin 1 receptor. Dynamics of interleukin 1 binding and internalization in T cells and fibroblasts.
In this study, we have demonstrated that a murine T cell lymphoma, EL 4, and a murine fibroblast cell line, Swiss 3T3, possess a single class of high affinity interleukin 1 (IL 1) receptors that exist in a dynamic state of equilibrium that is influenced by IL 1. In the absence of IL 1, the IL 1 receptor appears to turnover with a t1/2 of approximately 11 hr. However, when cells are incubated in the presence of IL 1, the IL 1 receptor undergoes extensive ligand-induced down-regulation. IL 1 itself is internalized at 37 degrees C; 50% of the surface-bound IL 1 is internalized in 60 to 120 min. IL 1 does not undergo degradation for at least 6 hr after internalization. By using electron microscopy and autoradiography, we observed several important features of the internalization process. When cells having bound 125I-IL 1 at 4 degrees C were shifted to 37 degrees C, IL 1 moved from the cell membrane to the cytoplasm where it was found in proximity to nuclei or within lysosomes. IL 1 appeared to progressively accumulate in nuclei. Six hours after shifting cells to 37 degrees C, 30 to 35% of the internalized 125I-IL 1 is associated with the cell nucleus. The accumulation of relatively high levels of IL 1 in the nucleus raises the interesting possibility that IL 1 may not only interact in a highly specific manner with cell surface receptors, but also with potentially important nuclear receptors.
D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004705:Endocytosis; D005347:Fibroblasts / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D008854:Microscopy, Electron; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D013601:T-Lymphocytes / Q000502:physiology*; D013696:Temperature
D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1