Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases.
Publication/Presentation Date
3-1-2002
Abstract
LPS induces an up-regulation of promatrix metalloproteinase-9 (proMMP9) gene expression in cells of the monocyte/macrophage lineage. We demonstrate here that LPS preparations are also able to activate proMMP9 made by human macrophages or THP-1 cells via LPS-associated proteinases, which cleave the N-terminal propeptide at a site or sites close to the one cleaved upon activation with organomercurial compounds. LPS-associated proteinases are serine proteinases that are able to cleave denatured collagens (gelatin) and the mammalian serine proteinase inhibitor, alpha(1)-proteinase inhibitor, thereby pushing the balance of extracellular matrix turnover even further toward degradation. A low molecular mass, low affinity inhibitor of MMP9, possibly derived from the propeptide, is generated during proMMP9 activation. However, inhibition of the LPS-associated proteinases had no effect on proMMP9 synthesis, indicating that their proteolytic activity was not required for signaling the up-regulation of the proMMP9 gene.
Volume
168
Issue
5
First Page
2449
Last Page
2455
ISSN
0022-1767
Published In/Presented At
Min, D., Moore, A. G., Bain, M. A., Breit, S. N., & Lyons, J. G. (2002). Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases. Journal of immunology (Baltimore, Md. : 1950), 168(5), 2449–2455. https://doi.org/10.4049/jimmunol.168.5.2449
Disciplines
Medicine and Health Sciences
PubMedID
11859137
Department(s)
Department of Surgery
Document Type
Article