Processing of interleukin-1 in cells of monocytic lineage is differentiation-dependent.
The interleukin-1 (IL-1) alpha and beta precursor proteins are processed and released from several cell types in the absence of a canonical signal peptide. To gain some insight into the mechanisms that allow the production of IL-1 alpha and beta, we have investigated by immunoprecipitation the synthesis, their release and processing in a promyeloblastic cell line of tumoral origin, U937, and in peripheral blood monocytes. We show that U937 monocytic cells, on induction with a tumor-promoting agent, synthesize and release into the culture medium proIL-1 beta but do not process it. Similarly, peripheral blood monocytes left in adherence for 24 h or longer, prior to addition of lipopolysaccharide, synthesize and release proIL-1 alpha and beta without detectable processing of either cytokine. Processing and release of IL-1 alpha and beta by peripheral blood monocytes can be observed when monocytes are left to adhere for periods less than 15 h before lipopolysaccharide addition. IL-1 alpha and beta show similar kinetics of release from the cells, suggesting the existence of a common mechanism regulating their secretion. Since peripheral blood monocytes left in adherence in the presence of lipopolysaccharide differentiate into macrophages, we conclude that release and processing of IL-1 can occur independently and that processing depends on the stage of differentiation of monocytes, i.e. only the monocytes at an early stage of differentiation produce 17-kDa IL-1 alpha and beta.
Carinci
V
V
Laboratory of Molecular Biology, Sclavo Research Center, Siena, Italy.
Guida
S
S
Fontana
M R
MR
Palla
E
E
Rossini
M
M
Melli
M
M
D002448:Cell Adhesion; D002454:Cell Differentiation; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors