DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts.
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.
Makino
Sachio
S
Division of Plastic and Reconstructive Surgery, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Mitsutake
Norisato
N
Nakashima
Masahiro
M
Saenko
Vladimir A
VA
Ohtsuru
Akira
A
Umezawa
Kazuo
K
Tanaka
Katsumi
K
Hirano
Akiyoshi
A
Yamashita
Shunichi
S
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
D001549:Benzamides; D024042:Collagen Type I; D003512:Cyclohexanones; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; C464444:dehydroxymethylepoxyquinomicin; D004247:DNA