title: Inhibition of MMP-2-Mediated Mast Cell Invasion by NF-κB Inhibitor DHMEQ in Mast Cells.
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.
authors: Innovation Center for Immunoregulation and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Naruto
authors: N
authors: Noma
authors: Masataka
authors: M
authors: Asagiri
authors: Masatoshi
authors: M
authors: Takeiri
authors: Saori
authors: S
authors: Ohmae
authors: Kenji
authors: K
authors: Takemoto
authors: Keiko
authors: K
authors: Iwaisako
authors: Nagahiro
authors: N
authors: Minato
authors: Mari
authors: M
authors: Maeda-Yamamoto
authors: Siro
authors: S
authors: Simizu
authors: Kazuo
authors: K
authors: Umezawa
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D003094:Collagen / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004338:Drug Combinations; D024202:Electrophoretic Mobility Shift Assay; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007797:Laminin / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology*; D020778:Matrix Metalloproteinase 2 / Q000276:immunology*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*; D011509:Proteoglycans / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D001549:Benzamides; D003512:Cyclohexanones; D004151:Dipeptides; D004338:Drug Combinations; D015850:Interleukin-6; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D016328:NF-kappa B; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; C464444:dehydroxymethylepoxyquinomicin; C059485:matrigel; D012313:RNA; D003094:Collagen; D020778:Matrix Metalloproteinase 2