In:
The Journal of Experimental Medicine, Rockefeller University Press, Vol. 185, No. 7 ( 1997-04-07), p. 1287-1294
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-1α 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.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.185.7.1287
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
1997
detail.hit.zdb_id:
1477240-1
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