title: Human vascular smooth muscle cells express interleukin-1beta-converting enzyme (ICE), but inhibit processing of the interleukin-1beta precursor by ICE.
abstract: Local immunoregulatory processes during normal vascular biology or pathogenesis are mediated in part by the production of and response to cytokines by vessel wall cells. Among these cytokines interleukin (IL)-1 is considered to be of major importance. Although vascular smooth muscle (SMC) and endothelial cells (EC) expressed both IL-1alpha and IL-1beta as cell-associated, 33-kilodalton (kD) precursors, SMC neither contained detectable mature IL-1beta, nor processed recombinant IL-1beta precursor into its mature 17-kD form. Thus, we investigated the expression and function of IL-1beta-converting enzyme (ICE) in vascular cells. We demonstrate in processing experiments with recombinant IL-1 precursor molecules that EC processed IL-1beta, in contrast to SMC. Despite the failure of SMC to process IL-1beta, these cells expressed ICE mRNA, immunoreactive ICE protein, and the expected IL-1beta nucleotide sequence. The lack of processing was explained by our finding that extracts of SMC specifically and concentration dependently blocked processing of IL-1beta precursor by recombinant or native ICE. The initial biochemical characterization of the inhibitory activity showed that it is heat-labile, has a molecular size of 50-100 kD, and is associated to the cell membrane compartment. Inhibition of processing, i.e., activation of IL-1beta precursor by SMC may constitute a novel regulatory mechanism during normal vascular biology or pathogenesis of vascular diseases.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, Center for Medicine and Biosciences, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schönbeck
authors.forename: M
authors.initials: M
authors.lastname: Herzberg
authors.forename: A
authors.initials: A
authors.lastname: Petersen
authors.forename: C
authors.initials: C
authors.lastname: Wohlenberg
authors.forename: J
authors.initials: J
authors.lastname: Gerdes
authors.forename: H D
authors.initials: HD
authors.lastname: Flad
authors.forename: H
authors.initials: H
authors.lastname: Loppnow
mesh_terms: D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D011498:Protein Precursors; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases; D020170:Caspase 1