title: DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts.
abstract: BACKGROUND
  Keloid is a benign dermal tumor characterized by proliferation of dermal fibroblasts and overproduction of extracellular matrix (ECM). Nuclear factor kappaB (NF-kappaB) plays an important role in regulation of inflammation, immune response and cell proliferation. Activation of the NF-kappaB pathway is thought to be closely linked to abnormal cell proliferation and ECM production in keloid fibroblasts.
  
  
  OBJECTIVE
  This study was set out to investigate the effects of a novel selective NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on keloid fibroblasts.
  
  
  METHODS
  Primary normal and keloid dermal fibroblasts were used for this study. NF-kappaB activity was assessed by DNA-binding assay and immunohistochemistry. The effect of DHMEQ was evaluated by cell viability, cell growth and type I collagen accumulation.
  
  
  RESULTS
  Basal NF-kappaB activity was constitutively elevated in keloid fibroblasts, indicating that this pathway is involved in keloid pathogenesis. DHMEQ markedly reduced cell proliferation and type I collagen accumulation in keloid fibroblasts.
  
  
  CONCLUSIONS
  The inhibition of NF-kappaB by DHMEQ may be an attractive therapeutic approach for keloids.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Makino
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umezawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D001549:Benzamides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D003512:Cyclohexanones / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001549:Benzamides; D024042:Collagen Type I; D003512:Cyclohexanones; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; C464444:dehydroxymethylepoxyquinomicin; D004247:DNA