© The Rockefeller University Press, 0022-1007/1997/4/1287/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 7, April 7, 1997 1287-1294
Human Vascular Smooth Muscle Cells Express Interleukin-1β–converting Enzyme (ICE), but Inhibit Processing of the Interleukin-1β Precursor by ICE
Uwe Schönbeck*,
Mona Herzberg*,
Arnd Petersen
,
Claudia Wohlenberg*,
Johannes Gerdes*,
Hans-Dieter Flad*, and
Harald Loppnow*
From the * Department of Immunology and Cell Biology, and Department of Clinical Medicine, Research Center Borstel, Center for Medicine and Biosciences, 23845 Borstel, Germany
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-1
and IL-1β as cell-associated, 33-kilodalton (kD) precursors, SMC neither contained detectable mature IL-1β, nor processed recombinant IL-1β precursor into its mature 17-kD form. Thus, we investigated the expression and function of IL-1β–converting enzyme (ICE) in vascular cells. We demonstrate in processing experiments with recombinant IL-1 precursor molecules that EC processed IL-1β, in contrast to SMC. Despite the failure of SMC to process IL-1β, these cells expressed ICE mRNA, immunoreactive ICE protein, and the expected IL-1β nucleotide sequence. The lack of processing was explained by our finding that extracts of SMC specifically and concentration dependently blocked processing of IL-1β 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-1β precursor by SMC may constitute a novel regulatory mechanism during normal vascular biology or pathogenesis of vascular diseases.
Address correspondence to Dr. H. Loppnow, Department of Immunology and Cell Biology, Center for Medicine and Biosciences, Research Center Borstel, Parkallee 22, 23845 Borstel, Germany. U. Schönbeck's present address is Vascular Medicine and Atherosclerosis Unit, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Ave., Boston, MA 02115.
1Abbreviations used in this paper: EC, endothelial cells; ICE, IL-1β–converting enzyme; RT, reverse transcription; SMC, smooth muscle cells.
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