Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells

Int Arch Allergy Immunol. 2015;166(2):84-90. doi: 10.1159/000371419. Epub 2015 Mar 13.

Abstract

Background: Stimulation with antigen and IgE is known to activate NF-κB in mast cells. In the present research, we studied the role of NF-κB on cellular migration in mast cell-like RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) using the NF-κB inhibitor (-)-DHMEQ.

Methods: A Matrigel invasion chamber was used to evaluate cell migration. A PCR array was used to screen the expression of 84 key genes involved in cell migration.

Results: (-)-DHMEQ inhibited antigen/IgE-induced NF-κB activation and expressions of its target genes such as IL-6 and TNF-α. (-)-DHMEQ was found to inhibit in vitro invasion toward the antigen without any toxicity. We then looked for NF-κB-dependent genes that would be important for mast cell invasion using the PCR array. (-)-DHMEQ was found to lower the expression of matrix metalloproteinase (MMP)-2. The MMP inhibitor GM6001 also inhibited cellular invasion toward the antigen. These effects of (-)-DHMEQ were obtained in both RBL-2H3 cells and BMMCs.

Conclusions: These findings indicate that (-)-DHMEQ suppressed mast cell migration via the inhibition of NF-κB-regulated MMP-2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Collagen / pharmacology
  • Cyclohexanones / pharmacology*
  • Dipeptides / pharmacology
  • Drug Combinations
  • Electrophoretic Mobility Shift Assay
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Laminin / pharmacology
  • Mast Cells / drug effects*
  • Mast Cells / immunology*
  • Matrix Metalloproteinase 2 / immunology*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology*
  • Proteoglycans / pharmacology
  • RNA / chemistry
  • RNA / genetics
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Benzamides
  • Cyclohexanones
  • Dipeptides
  • Drug Combinations
  • Interleukin-6
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • NF-kappa B
  • Proteoglycans
  • Tumor Necrosis Factor-alpha
  • dehydroxymethylepoxyquinomicin
  • matrigel
  • RNA
  • Collagen
  • Matrix Metalloproteinase 2