Interleukin‐6 (IL‐6) mediates pleiotropic functions through specific receptors (IL‐6R) composed of an 80‐kDa binding protein, associated with a non‐ligand binding protein (gp130) which transduces the signal. Because IL‐6 is the major tumor growth factor in multiple myeloma, we investigated the regulation of IL‐6R in two human multiple myeloma cell lines. Binding experiments with 125I‐labeled IL‐6 showed that IL‐6R were expressed at a high density on RPMI‐8226 cells (15 000 receptors/cell), but no specific binding was detected on XG‐1 cells, whose growth depends on the presence of exogenous IL‐6. However, when IL‐6 was removed from the culture medium, high‐affinity IL‐6R appeared on the surface of XG‐1 cells (5300 sites/cell). Treatment of RPMI‐8226 cells with IL‐6 reduced the number of IL‐6R without changing their affinity. This reduction was dose dependent and was not affected by acid treatment which dissociates ligand‐receptor complexes. Cross‐linking experiments showed that the formation of one IL‐6/receptor complex of 160 kDa markedly decreased upon IL‐6 treatment, while the other complex of 190 kDa became undetectable. These data provide evidence for ligand‐induced down‐regulation of membrane IL‐6R expression in myeloma cells. Treatment of RPMI‐8226 cells with interferon‐α (IFN‐α), which inhibits the growth of these cells, stimulated IL‐6R expression and increased the formation of the 160‐kDa IL‐6/receptor complex. This stimulation was specific for IFN‐α, since IFN‐γ reduced the number of IL‐6R. These data indicate that, in myeloma cells, IL‐6R are differentially regulated by IL‐6 and IFN‐α.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Interleukin‐6 receptors
- Multiple myeloma