Proteolysis of the native murine IL 1 beta precursor is required to generate IL 1 beta bioactivity.
We utilized antisera specific for murine IL 1 alpha and IL 1 beta proteins to characterize cell-associated IL 1 according to two distinct criteria, immunochemical detection of radiolabeled IL 1 polypeptides and inhibition of IL 1 activity in cell lysates. Evidence is presented that IL 1 alpha and IL 1 beta are each synthesized by LPS-stimulated but not by unstimulated murine macrophages and accumulate within the cell as intracellular precursors in sizes of 33 kDa and 37 kDa, respectively. As judged by the respective rates of synthesis, IL 1 alpha was about 4-fold more abundant than IL 1 beta. Most (greater than or equal to 95%) of the cell-associated IL 1 activity was inhibited in the presence of the antiserum to IL 1 alpha, suggesting that the precursor of IL 1 beta is mostly biologically inactive. Incubation of cell lysates with papain but not with trypsin or plasmin markedly stimulates an increase in the level of cell-associated IL 1 beta activity and leads to the cleavage of 15-16 kDa carboxyl-terminal fragments from the IL 1 beta precursor. Together, these data indicate that proteolysis of the IL 1 beta precursor is required to generate bioactive IL 1 beta molecules and provide a basis for further investigations of the specific role of proteinases in processing the IL 1 beta precursor to a bioactive form.
Günther
C
C
Institut of Clinical Microbiology, University Erlangen-Nürnberg, Federal Republic of Germany.
Röllinghoff
M
M
Beuscher
H U
HU
D000818:Animals; D005260:Female; D007106:Immune Sera; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010447:Peptide Hydrolases / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D007106:Immune Sera; D007375:Interleukin-1; D011498:Protein Precursors; C043830:interleukin 1 precursor; D010447:Peptide Hydrolases