PMID- 17884817
OWN - NLM
STAT- MEDLINE
DCOM- 20080103
LR  - 20220311
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 46
DP  - 2007 Nov 16
TI  - Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced 
      increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by 
      synovial cells.
PG  - 33714-33724
LID - S0021-9258(20)71707-2 [pii]
LID - 10.1074/jbc.M704041200 [doi]
AB  - Chronic hypoxia and inflammatory cytokines are hallmarks of inflammatory joint 
      diseases like rheumatoid arthritis (RA), suggesting a link between this 
      microenvironment and central pathological events. Because TACE/ADAM17 is the 
      predominant protease catalyzing the release of tumor necrosis factor alpha 
      (TNFalpha), a cytokine that triggers a cascade of events leading to RA, we 
      examined the regulation of this metalloprotease in response to hypoxia and 
      TNFalpha itself. We report that low oxygen concentrations and TNFalpha enhance 
      TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible 
      factor-1 (HIF-1) to the 5' promoter region. This is associated with elevated TACE 
      activity as shown by the increase in TNFalpha shedding rate. By the use of 
      HIF-1-deficient cells and by obliterating NF-kappaB activation, it was determined 
      that the hypoxic TACE response is mediated by HIF-1 signaling, whereas the 
      regulation by TNFalpha also requires NF-kappaB activation. As a support for the 
      in vivo relevance of the HIF-1 axis for TACE regulation, immunohistological 
      analysis of TACE and HIF-1 expression in RA synovium indicates that TACE is 
      up-regulated in both fibroblast- and macrophage-like synovial cells where it 
      localizes with elevated expression of both HIF-1 and TNFalpha. These findings 
      suggest a mechanism by which TACE is increased in RA-affected joints. They also 
      provide novel mechanistic clues on the influence of the hypoxic and inflammatory 
      microenvironment on joint diseases.
FAU - Charbonneau, Martine
AU  - Charbonneau M
AD  - Immunology Division, Departments of Pediatrics.
FAU - Harper, Kelly
AU  - Harper K
AD  - Immunology Division, Departments of Pediatrics.
FAU - Grondin, Francine
AU  - Grondin F
AD  - Immunology Division, Departments of Pediatrics.
FAU - Pelmus, Manuela
AU  - Pelmus M
AD  - Department of Pathology, Universite de Sherbrooke, Quebec, J1H 5N4, Canada.
FAU - McDonald, Patrick P
AU  - McDonald PP
AD  - Medicine, Faculty of Medicine, Universite de Sherbrooke, Quebec J1H 5N4, Canada.
FAU - Dubois, Claire M
AU  - Dubois CM
AD  - Immunology Division, Departments of Pediatrics. Electronic address: 
      Claire.M.Dubois@usherbrooke.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070919
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (Adam17 protein, mouse)
RN  - EC 3.4.24.86 (Adam17 protein, rat)
SB  - IM
MH  - ADAM Proteins/*physiology
MH  - ADAM17 Protein
MH  - Animals
MH  - Arthritis, Rheumatoid/metabolism
MH  - Base Sequence
MH  - Female
MH  - Fibroblasts/metabolism
MH  - *Gene Expression Regulation
MH  - *Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Signal Transduction
MH  - Synovial Membrane/cytology/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2007/09/22 09:00
MHDA- 2008/01/04 09:00
CRDT- 2007/09/22 09:00
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2008/01/04 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
AID - S0021-9258(20)71707-2 [pii]
AID - 10.1074/jbc.M704041200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Nov 16;282(46):33714-33724. doi: 10.1074/jbc.M704041200. Epub 
      2007 Sep 19.