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Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-κB1, but not RelA in normal human dermal fibroblast cells

M Vandermeeren, Sophie Janssens UGent, Hilde Wouters, Inge Borghmans, Marcel Borgers, Rudi Beyaert UGent and Johan Geysen (2001) JOURNAL OF INVESTIGATIVE DERMATOLOGY. 116(1). p.124-130
abstract
We previously demonstrated that the oral antipsoriatic dimethylfumarate is an inhibitor of cytokine-induced adhesion molecule expression in endothelial HUVEC cells. We now report the inhibitory effect of dimethylfumarate on tumor-necrosis-factor-alpha- or interleukin-1 alpha -induced intercellular adhesion molecule 1 expression in normal human dermal fibroblasts. Western blots of normal human dermal fibroblast cytoplasmic extracts showed that dimethylfumarate has minor effects on the I kappaB alpha, beta and epsilon proteins: their cytokine-induced degradation and resynthesis is only slowed down, an effect most prominently observed for I kappaB beta. No inhibitory effect of dimethylfumarate was observed on cytokine-induced RelA/p65 or c-Rel accumulation in nuclear extracts of cytokine-treated normal human dermal fibroblast cells. In contrast, cytokine-induced nuclear factor beta B1/p50 nuclear accumulation was specifically inhibited by dimethylfumarate. This inhibitory effect on nuclear factor kappa B1 nuclear localization in normal human dermal fibroblasts proved sufficient to inhibit nuclear factor kappa B1-RelA binding to nuclear factor kappaB consensus oligonucleotides in DNA binding assays. Likewise, cytokine-induced activation of a pNF kappaB::luciferase reporter construct in transiently transfected normal human dermal fibroblasts was inhibited by dimethylfumarate. The observations support a mechanistic model for the oral antipsoriatic dimethylfumarate in which lowering of nuclear factor kappa B1 leads to changes in the nuclear factor kappa B1-ReLA nuclear balance and inhibition of cytokine-induced adhesion molecule expression in normal human dermal fibroblasts.
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author
organization
alternative title
Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-kappa B1, but not RelA in normal human dermal fibroblast cells
year
type
journalArticle (original)
publication status
published
subject
keyword
psoriasis, ICAM-1, p50, p65, NF-KAPPA-B, TUMOR-NECROSIS-FACTOR, FUMARIC-ACID DERIVATIVES, HUMAN ENDOTHELIAL-CELLS, GENE-EXPRESSION, TRANSCRIPTIONAL ACTIVITY, ALPHA PROTEOLYSIS, EPITHELIAL-CELLS, CROSS-TALK, ACTIVATION
journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
J. Invest. Dermatol.
volume
116
issue
1
pages
124 - 130
Web of Science type
Article
Web of Science id
000166797200016
JCR category
DERMATOLOGY
JCR impact factor
4.645 (2001)
JCR rank
1/38 (2001)
JCR quartile
1 (2001)
ISSN
0022-202X
DOI
10.1046/j.1523-1747.2001.00211.x
language
English
UGent publication?
yes
classification
A1
additional info
the second and the third author are equally contributing authors
copyright statement
I have transferred the copyright for this publication to the publisher
id
140111
handle
http://hdl.handle.net/1854/LU-140111
date created
2004-01-14 13:37:00
date last changed
2016-12-19 15:38:06
@article{140111,
  abstract     = {We previously demonstrated that the oral antipsoriatic dimethylfumarate is an inhibitor of cytokine-induced adhesion molecule expression in endothelial HUVEC cells. We now report the inhibitory effect of dimethylfumarate on tumor-necrosis-factor-alpha- or interleukin-1 alpha -induced intercellular adhesion molecule 1 expression in normal human dermal fibroblasts. Western blots of normal human dermal fibroblast cytoplasmic extracts showed that dimethylfumarate has minor effects on the I kappaB alpha, beta and epsilon proteins: their cytokine-induced degradation and resynthesis is only slowed down, an effect most prominently observed for I kappaB beta. No inhibitory effect of dimethylfumarate was observed on cytokine-induced RelA/p65 or c-Rel accumulation in nuclear extracts of cytokine-treated normal human dermal fibroblast cells. In contrast, cytokine-induced nuclear factor beta B1/p50 nuclear accumulation was specifically inhibited by dimethylfumarate. This inhibitory effect on nuclear factor kappa B1 nuclear localization in normal human dermal fibroblasts proved sufficient to inhibit nuclear factor kappa B1-RelA binding to nuclear factor kappaB consensus oligonucleotides in DNA binding assays. Likewise, cytokine-induced activation of a pNF kappaB::luciferase reporter construct in transiently transfected normal human dermal fibroblasts was inhibited by dimethylfumarate. The observations support a mechanistic model for the oral antipsoriatic dimethylfumarate in which lowering of nuclear factor kappa B1 leads to changes in the nuclear factor kappa B1-ReLA nuclear balance and inhibition of cytokine-induced adhesion molecule expression in normal human dermal fibroblasts.},
  author       = {Vandermeeren, M and Janssens, Sophie and Wouters, Hilde and Borghmans, Inge and Borgers, Marcel and Beyaert, Rudi and Geysen, Johan},
  issn         = {0022-202X},
  journal      = {JOURNAL OF INVESTIGATIVE DERMATOLOGY},
  keyword      = {psoriasis,ICAM-1,p50,p65,NF-KAPPA-B,TUMOR-NECROSIS-FACTOR,FUMARIC-ACID DERIVATIVES,HUMAN ENDOTHELIAL-CELLS,GENE-EXPRESSION,TRANSCRIPTIONAL ACTIVITY,ALPHA PROTEOLYSIS,EPITHELIAL-CELLS,CROSS-TALK,ACTIVATION},
  language     = {eng},
  number       = {1},
  pages        = {124--130},
  title        = {Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-\ensuremath{\kappa}B1, but not RelA in normal human dermal fibroblast cells},
  url          = {http://dx.doi.org/10.1046/j.1523-1747.2001.00211.x},
  volume       = {116},
  year         = {2001},
}

Chicago
Vandermeeren, M, Sophie Janssens, Hilde Wouters, Inge Borghmans, Marcel Borgers, Rudi Beyaert, and Johan Geysen. 2001. “Dimethylfumarate Is an Inhibitor of Cytokine-induced Nuclear Translocation of NF-κB1, but Not RelA in Normal Human Dermal Fibroblast Cells.” Journal of Investigative Dermatology 116 (1): 124–130.
APA
Vandermeeren, M, Janssens, S., Wouters, H., Borghmans, I., Borgers, M., Beyaert, R., & Geysen, J. (2001). Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-κB1, but not RelA in normal human dermal fibroblast cells. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 116(1), 124–130.
Vancouver
1.
Vandermeeren M, Janssens S, Wouters H, Borghmans I, Borgers M, Beyaert R, et al. Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-κB1, but not RelA in normal human dermal fibroblast cells. JOURNAL OF INVESTIGATIVE DERMATOLOGY. 2001;116(1):124–30.
MLA
Vandermeeren, M, Sophie Janssens, Hilde Wouters, et al. “Dimethylfumarate Is an Inhibitor of Cytokine-induced Nuclear Translocation of NF-κB1, but Not RelA in Normal Human Dermal Fibroblast Cells.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 116.1 (2001): 124–130. Print.