Anti-inflammatory Property of β-D-Mannuronic Acid (M2000) on Expression and Activity of Matrix Metalloproteinase-2 and -9 through CD147 Molecule in Phorbol Myristate Acetate-differentiated THP-1 Cells

Iran J Allergy Asthma Immunol. 2017 Oct;16(5):443-451.


The aim of this study was to evaluate the effects of M2000, a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property and without gastro-nephrotoxicitic effects on matrix metalloproteinases (MMP)-2 and (MMP)-9 in phorbol myristate acetate (PMA)-differentiated THP-1 cells. Gene expression and activity of MMP-2 and MMP-9 are inhibited respectively by the tissue inhibitor of matrix metalloproteinase (TIMP)-2 and (TIMP)-1 and are induced by extracellular matrix metalloproteinase inducer (CD147/EMMPRIN). In this study, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine gene expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Flow cytometry and zymography were applied to determine cellular surface expression of CD147 and activity of MMP-2 and MMP-9, respectively. Our results showed that treatment of THP-1 cells with high concentration (25 µg/mL) of M2000 significantly decreased the cellular surface expression of CD147 (p<0.05) and the gene expression of MMP-2, MMP-9 and TIMP-1 (p<0.05), and inhibited the gelatinolytic activity of MMP-2 and MMP-9 (p<0.05). According to our results, M2000 can reduce inflammation through inhibition of the cellular surface expression of CD147 and decrease the gene expression and gelatinolytic activity of MMP-2 and MMP-9 in PMA-differentiated THP-1 cells.

Keywords: CD147; Mannuronic acid; Matrix metalloproteinases; Tissue inhibitor of matrix metalloproteinase.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Basigin / metabolism
  • Cell Differentiation / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Enzyme Activation
  • Gene Expression Regulation / drug effects*
  • Hexuronic Acids / pharmacology*
  • Humans
  • Immunophenotyping
  • Macrophage Activation
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • THP-1 Cells
  • Tetradecanoylphorbol Acetate / immunology


  • Anti-Inflammatory Agents
  • Hexuronic Acids
  • Basigin
  • mannuronic acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate