Identification of a biologically functional novel IL-1 beta-specific receptor on adult rat hepatocytes.
Cellular receptors for interleukin-1 (IL-1) bind both IL-1 alpha and IL-1 beta with the same affinity, and both IL-1 alpha and IL-1 beta 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-1 beta but not IL-1 alpha, present on adult rat hepatocytes. Scatchard analysis of the binding of 125I-IL-1 beta to isolated adult rat hepatocytes showed that rat hepatocytes express a high affinity receptor for IL-1 beta with a Kd value of 9.6 x 10(-10) M at 1,200 sites/cell, whereas there was no specific binding of 125I-IL-1 alpha at least up to 10 ng/ml. Specific binding of 125I-IL-1 beta to hepatocytes was competitively inhibited by unlabeled IL-1 beta, but not by IL-1 alpha. Cross-linking of 125I-IL-1 beta to plasma membranes of hepatocytes indicated that the receptor for IL-1 beta has an apparent molecular mass of 80-100 kDa. Moreover, the formation of a cross-linked complex between 125I-IL-1 beta and the receptor was specifically inhibited by unlabeled IL-1 beta, but not by IL-1 alpha. Finally, DNA synthesis of adult rat hepatocytes was specifically inhibited by IL-1 beta, but not by IL-1 alpha, in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Kohira
T
T
Division of Biochemistry, Osaka University Medical School.
Matsumoto
K
K
Ichihara
A
A
Nakamura
T
T
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D004247:DNA