Identification of a Biologically Functional Novel IL-1β-Specific Receptor on Adult Rat Hepatocytes

• Published in: Journal of biochemistry (Tokyo) Vol. 114; no. 5; pp. 658 - 662
• Main Authors: Kohira, Terutomo, Matsumoto, Kunio, Ichihara, Akira, Nakamura, Toshikazu
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.1993
• Subjects: 3T3 Cells; Animals; Binding, Competitive; Biological and medical sciences; Cell Division - drug effects; Cell Membrane - metabolism; Cell receptors; Cell structures and functions; Cells, Cultured; DNA - biosynthesis; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Interleukin-1 - metabolism; Interleukin-1 - pharmacology; Liver - cytology; Liver - metabolism; Mice; Molecular and cellular biology; Molecular Weight; Rats; Rats, Wistar; Receptors, Interleukin-1 - metabolism; Recombinant Proteins - metabolism; Vertebrata; Mammalia; Binding capacity; Hepatocyte; Rat; Cytokine; Rodentia; Interleukin 1β; Molecular cloning; Biological receptor
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a124233

Cellular receptors for interleukin-1 (IL-1) bind both IL-1α and IL-1β with the same affinity, and both IL-1α and IL-1β have the same potential in most IL-1-related biological responses, despite their low amino acid sequence homology (26%). Here, we identified and partially characterized a biologically functional novel IL-1 receptor, which specifically binds IL-1β but not IL-1α, present on adult rat hepatocytes. Scatchard analysis of the binding of 125I-IL-1β to isolated adult rat hepatocytes showed that rat hepatocytes express a high afiinity receptor for IL-1β with a Kd value of 9.6×10−10 M at 1, 200 sites/cell, whereas there was no specific binding of 125I-IL-1α at least up to l0ng/ml. Specific binding of 125I-IL-1β to hepatocytes was competitively inhibited by unlabeled IL-1β, but not by IL-1α. Cross-linking of 125I-IL-1β to plasma membranes of hepatocytes indicated that the receptor for IL-1β has an apparent molecular mass of 80–100 kDa. Moreover, the formation of a cross-linked complex between 125I-IL-1β and the receptor was specifically inhibited by unlabeled IL-1β, but not by IL-1α. Finally, DNA synthesis of adult rat hepatocytes was specifically inhibited by IL-1β, but not by IL-1α, in a dose-dependent manner. Therefore, (i) adult rat hepatocytes express a novel type of IL-1 receptor, i.e, the IL-1β-specific receptor; and (ii) this IL-1β-specific receptor is biologically functional, being relevant to the specific inhibitory activity of IL-1β on growth of rat hepatocytes.