PMID- 12885946
OWN - NLM
STAT- MEDLINE
DCOM- 20030909
LR  - 20231213
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 74
IP  - 2
DP  - 2003 Aug
TI  - Pathways for the regulation of interferon-gamma-inducible genes by iron in human 
      monocytic cells.
PG  - 287-94
AB  - To elucidate iron-regulated interferon-gamma (IFN-gamma) effector functions, we 
      investigated three IFN-gamma-inducible genes [intercellular adhesion molecule-1 
      (ICAM-1), human leukocyte antigen (HLA)-DR, guanosine 
      5'-triphosphate-cyclohydrolase I (GTP-CH)] in primary human monocytes and the 
      cell line THP-1. IFN-gamma increased the surface expression of ICAM-1 and HLA-DR 
      and stimulated GTP-CH activity. Addition of iron before cytokine stimulation 
      resulted in a dose-dependent reduction of these pathways, and iron restriction by 
      desferrioxamine (DFO) enhanced ICAM-1, HLA-DR, and GTP-CH expression. Iron 
      neither affected IFN-gamma binding to its receptor nor IFN-gamma receptor surface 
      expression. IFN-gamma-inducible mRNA expression of ICAM-1, HLA-DR, and GTP-CH was 
      reduced by iron and increased by DFO by a transcriptional mechanism. Moreover, 
      ICAM-1 and to a lesser extent, GTP-CH and HLA-DR mRNA expression were regulated 
      post-transcriptionally, as iron pretreatment resulted in shortening the mRNA 
      half-life compared with cells treated with IFN-gamma alone. Thus, iron 
      perturbations regulate IFN-gamma effector pathways by transcriptional and 
      post-transcriptional mechanisms, indicating that iron rather interferes with 
      IFN-gamma signal-transduction processes.
FAU - Oexle, Horst
AU  - Oexle H
AD  - Department of Internal Medicine, University Hospital Innsbruck, Austria.
FAU - Kaser, Arthur
AU  - Kaser A
FAU - Most, Johannes
AU  - Most J
FAU - Bellmann-Weiler, Rosa
AU  - Bellmann-Weiler R
FAU - Werner, Ernst R
AU  - Werner ER
FAU - Werner-Felmayer, Gabriele
AU  - Werner-Felmayer G
FAU - Weiss, Gunter
AU  - Weiss G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interferon-Stimulated Gene Factor 3)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Receptors, Interferon)
RN  - 0 (Transcription Factors)
RN  - 0 (gamma interferon activation factor)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 63231-63-0 (RNA)
RN  - 82115-62-6 (Interferon-gamma)
RN  - E1UOL152H7 (Iron)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Deferoxamine/pharmacology
MH  - GTP Cyclohydrolase/genetics/*metabolism
MH  - HLA-DR Antigens/genetics/*metabolism
MH  - Half-Life
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics/*metabolism
MH  - Interferon-Stimulated Gene Factor 3
MH  - Interferon-gamma/*pharmacology
MH  - Iron/pharmacology
MH  - Iron Chelating Agents/pharmacology
MH  - Monocytes/enzymology/*metabolism/physiology
MH  - Phosphorylation/drug effects
MH  - Protein Binding
MH  - RNA/chemistry/metabolism
MH  - Receptors, Interferon/*metabolism
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - Interferon gamma Receptor
EDAT- 2003/07/30 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/07/30 05:00
PHST- 2003/07/30 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/07/30 05:00 [entrez]
AID - 10.1189/jlb.0802420 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Aug;74(2):287-94. doi: 10.1189/jlb.0802420.