Interleukin-1 binding, internalization, and processing in a murine osteoblastic cell line, MC3T3.E1.
We have investigated the interaction of IL-1 and its receptor on a murine osteoblastic cell line, MC3T3.E1, with regard to binding, internalization, and the fate of the receptor-ligand complex following internalization. Binding experiments indicated that this cell line possesses a high affinity receptor (Kd 1.02 x 10(-10) M) that binds both IL-1 alpha and IL-1 beta, and has approximately 6500 receptors per cell. Cross-linking experiments indicated that the receptor has a molecular weight of 100,000 daltons. Binding of IL-1 to the receptor is inhibited by the Interleukin Receptor Antagonist Protein (IRAP). These characteristics suggest that the murine osteoblastic receptor resembles that found on T lymphocytes and fibroblasts. Internalization experiments showed that this process is fairly rapid and results in degradation of the ligand and subsequent loss of degraded IL-1 from the cell. In this respect, processing of the receptor-ligand complex mimics that observed with IL-1 receptors on murine bone marrow cells, pre-B cells, and macrophages. Although the reasons for these differences are unclear, it may be that, unlike fibroblasts, osteoblasts may function as an effector cell which rapidly removes IL-1 from the immediate environment via ligand degradation while at the same time initiating bone resorption via stimulation of osteopontin biosynthesis.
Shelly
J A
JA
Upjohn Laboratories, Upjohn Company, Kalamazoo, Mi 49001.
Laborde
A L
AL
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D010006:Osteoblasts / Q000378:metabolism*; D011485:Protein Binding; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology; D012886:Skull / Q000166:cytology
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins