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Lipopolysaccharide activates caspase-1 (interleukin-1-converting enzyme) in cultured monocytic and endothelial cells

Item Type:Article
Title:Lipopolysaccharide activates caspase-1 (interleukin-1-converting enzyme) in cultured monocytic and endothelial cells
Creators Name:Schumann, R.R. and Belka, C. and Reuter, D. and Lamping, N. and Kirschning, C. and Weber, J.R. and Pfeil, D.
Abstract:Interleukin-1 beta (IL-1 beta) is a pleiotropic proinflammatory cytokine. Mechanisms leading to its secretion include not only release of newly synthesized protein, but also cleavage of a preformed immature precursor protein into an active secretory form by the intracellular protease caspase-1 (formerly termed IL-1-converting enzyme [ICE]). Caspase-1 belongs to a rapidly growing family of cysteine proteases with substrate specificity for aspartate involved in cellular apoptosis. We have used an assay determining the caspase-1 activity based on cleavage of a fluorogenic peptide substrate to elucidate its role in lipopolysaccharide (LPS)-induced secretion of IL-1 beta. We show that LPS induces moderate caspase-1 activity in the monocytic cell line THP-1, in freshly isolated peripheral blood monocytes, and in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent fashion. Caspase-1 activation by LPS was associated with cleavage of the IL-1 beta precursor protein that was followed by release of the mature IL-1 beta protein in monocytic cells. In contrast, subsequent release of IL-1 beta by HUVECs was not significant. LPS-induced caspase-1 activation appeared not to result from modulation of caspase-1 transcript accumulation and inhibition of caspase-1 activity was accomplished by two specific inhibitors, YVAD-CHO and YVAD-CMK, capable of alleviating the release of mature IL-1 beta. Taken together, these results show that LPS moderately activates caspase-1 and that caspase-1 activation contributes to LPS induction of IL-1 beta secretion.
Keywords:Caspase 1, Cultured Cells, Cysteine Endopeptidases, Vascular Endothelium, Enzyme Activation, Interleukin-1, Lipopolysaccharides, Monocytes
Publisher:American Society of Hematology
Page Range:577-584
Date:15 January 1998
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/91/2/577
PubMed:View item in PubMed

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