PMID- 15145954
OWN - NLM
STAT- MEDLINE
DCOM- 20040910
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 31
DP  - 2004 Jul 30
TI  - Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes 
      revealed using global transcriptional profiling.
PG  - 32633-42
AB  - Identification of tumor necrosis factor-alpha (TNF alpha) as the key agent in 
      inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and 
      psoriasis, led to TNF alpha-targeting therapies, which, although avoiding many of 
      the side-effects of previous drugs, nonetheless causes other side-effects, 
      including secondary infections and cancer. By controlling gene expression, TNF 
      alpha orchestrates the cutaneous responses to environmental damage and 
      inflammation. To define TNF alpha action in epidermis, we compared the 
      transcriptional profiles of normal human keratinocytes untreated and treated with 
      TNF alpha for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found 
      that TNF alpha regulates not only immune and inflammatory responses but also 
      tissue remodeling, cell motility, cell cycle, and apoptosis. Specifically, TNF 
      alpha regulates innate immunity and inflammation by inducing a characteristic 
      large set of chemokines, including newly identified TNF alpha targets, that 
      attract neutrophils, macrophages, and skin-specific memory T-cells. This 
      implicates TNF alpha in the pathogenesis of psoriasis, fixed drug eruption, 
      atopic and allergic contact dermatitis. TNF alpha promotes tissue repair by 
      inducing basement membrane components and collagen-degrading proteases. 
      Unexpectedly, TNF alpha induces actin cytoskeleton regulators and integrins, 
      enhancing keratinocyte motility and attachment, effects not previously associated 
      with TNF alpha. Also unanticipated was the influence of TNF alpha upon 
      keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes. 
      Therefore, TNF alpha initiates not only the initiation of inflammation and 
      responses to injury, but also the subsequent epidermal repair. The results 
      provide new insights into the harmful and beneficial TNF alpha effects and define 
      the mechanisms and genes that achieve these outcomes, both of which are important 
      for TNF alpha-targeted therapies.
FAU - Banno, Tomohiro
AU  - Banno T
AD  - Departments of Dermatology New York University School of Medicine, 550 First 
      Avenue, New York, New York 10016, USA.
FAU - Gazel, Alix
AU  - Gazel A
FAU - Blumenberg, Miroslav
AU  - Blumenberg M
LA  - eng
GR  - AR41850/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 - 20040515
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Actins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Complementary)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Northern
MH  - Cell Adhesion
MH  - Cell Death
MH  - Cell Division
MH  - Cell Lineage
MH  - Cell Movement
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Cytoskeleton/metabolism
MH  - Flow Cytometry
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation
MH  - Keratinocytes/cytology/metabolism
MH  - Kinetics
MH  - Macrophages/metabolism
MH  - Microscopy, Fluorescence
MH  - NF-kappa B/metabolism
MH  - Neutrophils/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Complementary/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - *Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Zinc Fingers
EDAT- 2004/05/18 05:00
MHDA- 2004/09/11 05:00
CRDT- 2004/05/18 05:00
PHST- 2004/05/18 05:00 [pubmed]
PHST- 2004/09/11 05:00 [medline]
PHST- 2004/05/18 05:00 [entrez]
AID - S0021-9258(20)77562-9 [pii]
AID - 10.1074/jbc.M400642200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Jul 30;279(31):32633-42. doi: 10.1074/jbc.M400642200. Epub 2004 
      May 15.