PMID- 15278366
OWN - NLM
STAT- MEDLINE
DCOM- 20050228
LR  - 20220331
IS  - 0340-3696 (Print)
IS  - 0340-3696 (Linking)
VI  - 296
IP  - 3
DP  - 2004 Aug
TI  - Activation of NFkappaB signal pathways in keloid fibroblasts.
PG  - 125-33
AB  - Keloids are characterized as an "over-exuberant" healing response resulting in a 
      disproportionate extracellular matrix (ECM) accumulation and tissue fibrosis. In 
      view of the integral role of inflammation and cytokines in the healing response, 
      it is logical to assume that they may play a part in orchestrating the pathology 
      of this "abnormal" healing process. Tumor necrosis factor-alpha (TNF-alpha) is a 
      potent proinflammatory cytokine involved in activation of signaling events and 
      transcriptional programs, such as NFkappaB. This study attempts to determine the 
      difference in NFkappaB and its related genes expression and DNA binding activity 
      between keloid and normal skin fibroblasts. Three keloid and normal skin tissues 
      (NSk) and their derived fibroblasts were used to determine NFkappaB signaling 
      pathway expression using specific cDNA microarrays, Western blot analysis and 
      immunohistochemistry. Electrophoretic mobility gel shift assay (EMSA) was used to 
      assess NFkappaB-binding activity, all assays were performed in the presence and 
      absence of TNF-alpha. TNF-alpha up-regulated 15% of NFkappaB signal pathway 
      related genes in keloid fibroblast compared to normal skin. At the protein level, 
      keloid fibroblasts and tissues showed higher basal levels of TNF- 
      receptor-associated factors-TRAF1, TRAF2-TNF-alpha, inhibitor of apoptosis 
      (c-IAP-1), and NFkappaB, compared with NSk. Keloid fibroblasts showed a 
      constitutive increase in NFkappaB-binding activity in comparison to NSk both with 
      and without TNF-alpha treatment. NFkappaB and its targeted genes, especially the 
      antiapoptotic genes, could play a role in keloid pathogenesis; targeting NFkappaB 
      could help in developing therapeutic interventions for the treatment of keloid 
      scarring.
FAU - Messadi, Diana V
AU  - Messadi DV
AD  - Section of Oral Medicine and Diagnosis, UCLA School of Dentistry, 10833 LeConte 
      Ave., CHS 63-01, Los Angeles, CA 90095, USA. dmessadi@dent.ucla.edu
FAU - Doung, Hai S
AU  - Doung HS
FAU - Zhang, Qhunzhou
AU  - Zhang Q
FAU - Kelly, A Paul
AU  - Kelly AP
FAU - Tuan, Tai-Lan
AU  - Tuan TL
FAU - Reichenberger, Ernst
AU  - Reichenberger E
FAU - Le, Anh D
AU  - Le AD
LA  - eng
GR  - 1S11 AR47359/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040728
PL  - Germany
TA  - Arch Dermatol Res
JT  - Archives of dermatological research
JID - 8000462
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Blotting, Western
MH  - Dermis/cytology
MH  - Fibroblasts/physiology
MH  - Humans
MH  - Keloid/*metabolism/*physiopathology
MH  - Male
MH  - NF-kappa B/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2004/07/28 05:00
MHDA- 2005/03/01 09:00
CRDT- 2004/07/28 05:00
PHST- 2004/02/17 00:00 [received]
PHST- 2004/03/05 00:00 [revised]
PHST- 2004/03/09 00:00 [accepted]
PHST- 2004/07/28 05:00 [pubmed]
PHST- 2005/03/01 09:00 [medline]
PHST- 2004/07/28 05:00 [entrez]
AID - 10.1007/s00403-004-0487-y [doi]
PST - ppublish
SO  - Arch Dermatol Res. 2004 Aug;296(3):125-33. doi: 10.1007/s00403-004-0487-y. Epub 
      2004 Jul 28.