Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases.

نویسندگان

  • Danqing Min
  • Anthony G Moore
  • Michael A Bain
  • Samuel N Breit
  • J Guy Lyons
چکیده

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.

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عنوان ژورنال:
  • Journal of immunology

دوره 168 5  شماره 

صفحات  -

تاریخ انتشار 2002