Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells

Biochem Biophys Res Commun. 2005 May 13;330(3):989-98. doi: 10.1016/j.bbrc.2005.03.069.


In the present study, we found that serum amyloid A (SAA) stimulated matrix-metalloproteinase-9 (MMP-9) upregulation at the transcription and translational levels in THP-1 cells. SAA stimulated the activation of nuclear factor kappaB (NF-kappaB), which was required for the MMP-9 upregulation by SAA. The signaling events induced by SAA included the activation of ERK and intracellular calcium rise, which were found to be required for MMP-9 upregulation. Formyl peptide receptor like 1 (FPRL1) was found to be involved in the upregulation of MMP-9 by SAA. Among several FPRL1 agonists, including Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), SAA selectively stimulated MMP-9 upregulation. With respect to the molecular mechanisms involved in the differential action of SAA and WKYMVm, we found that SAA could not competitively inhibit the binding of 125I-labeled WKYMVm to FPRL1. Taken together, we suggest that SAA plays a role in the modulation of inflammatory and immune responses via FPRL1, by inducing MMP-9 upregulation in human monocytic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Line
  • Enzyme Activation / drug effects
  • Enzyme Induction / drug effects
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Monocytes / drug effects*
  • Monocytes / metabolism*
  • NF-kappa B / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, Formyl Peptide / metabolism*
  • Receptors, Lipoxin / metabolism*
  • Serum Amyloid A Protein / pharmacology*
  • Signal Transduction / drug effects*
  • Transcription, Genetic / genetics


  • FPR2 protein, human
  • NF-kappa B
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • Serum Amyloid A Protein
  • Protein Serine-Threonine Kinases
  • Matrix Metalloproteinase 9
  • Calcium