Biological activity and receptor binding of human prointerleukin-1 beta and subpeptides.
We report here that the human interleukin-1 beta precursor (proIL-1 beta) protein as well as several interleukin-1 beta (IL-1 beta) subpeptides bind cellular receptors specifically and exhibit biological activity by stimulating proliferation of helper T-cells. IL-1 beta polypeptides have been synthesized by in vitro translation of mRNAs transcribed from plasmid vectors containing the bacteriophage SP6 promoter joined to the complete IL-1 beta cDNA or to deletion constructs. The quantity of IL-1 beta in vitro translation products was increased significantly by replacing the cognate IL-1 beta untranslated leader sequence with a 37-nucleotide plant viral untranslated leader. Translation of chimeric mRNAs followed by direct bioactivity assay demonstrated that mature IL-1 beta-(117-269), proIL-1 beta-(1-269), and peptide IL-1-(71-269) were all biologically active. Specific binding to cellular receptors was observed with these three IL-1 beta molecules; moreover, several peptides with minimal biological activity also bound receptor specifically. The biological activity and receptor binding properties of the IL-1 beta proteins reported here contrast with those described by Mosley et al. (Mosley, B., Urdal, D. L., Prickett, K. S., Larsen, A., Cosman, D., Conlon, P. J., Gillis, S., and Dower, S. K. (1987) J. Biol. Chem. 262, 2941-2944; Mosley, B., Dower, S. K., Gillis, S., and Cosman, D. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4572-4576), who reported that proIL-1 beta-(1-269) had no biological activity and does not bind receptor. Our results indicate that proIL-1 beta is active at a relatively high concentration, and analysis of the proIL-1 beta-(1-269) and IL-1-(71-269) bioactivity data suggests a possible relationship with membrane-bound IL-1.
Jobling
S A
SA
Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge 02139.
Auron
P E
PE
Gurka
G
G
Webb
A C
AC
McDonald
B
B
Rosenwasser
L J
LJ
Gehrke
L
L
D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000378:metabolism; D010957:Plasmids; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014158:Transcription, Genetic
D007375:Interleukin-1; D010446:Peptide Fragments; D011498:Protein Precursors; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; C043830:interleukin 1 precursor; D004247:DNA