PMID- 1617321
OWN - NLM
STAT- MEDLINE
DCOM- 19920804
LR  - 20081121
IS  - 0268-3369 (Print)
IS  - 0268-3369 (Linking)
VI  - 9
IP  - 5
DP  - 1992 May
TI  - Regulation of tumor necrosis factor-alpha production and gene expression in 
      monocytes.
PG  - 369-76
AB  - Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated 
      monocytes/macrophages, inhibits leukemic cell growth and may contribute to a 
      graft-versus-leukemia effect after marrow transplantation. We examined the 
      recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage 
      colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor 
      (M-CSF), alone or in combination, for their ability to induce monocytes from 
      normal donors and patients after marrow grafting to express TNF-alpha mRNA and 
      secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by 
      Percoll separation of E-rosette-negative cells, and cultured with cytokines under 
      non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable 
      in freshly isolated monocytes from normal donors. Only the combination of 
      IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA 
      transcript levels and protein secretion. Levels of TNF-alpha transcripts induced 
      by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to 
      lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak 
      after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of 
      inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In 
      contrast, greater than 80% of the total TNF-alpha bioactivity secreted by 
      LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were 
      incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, 
      both TNF-alpha mRNA expression and TNF-alpha protein production 
      occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Kohn, F R
AU  - Kohn FR
AD  - Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver, 
      Canada.
FAU - Phillips, G L
AU  - Phillips GL
FAU - Klingemann, H G
AU  - Klingemann HG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Bone Marrow Transplant
JT  - Bone marrow transplantation
JID - 8702459
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Blotting, Northern
MH  - Bone Marrow Transplantation
MH  - Cell Separation
MH  - Female
MH  - Gene Expression Regulation/*genetics
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Lipopolysaccharides/physiology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/*metabolism
MH  - RNA, Messenger/analysis/genetics
MH  - Time Factors
MH  - Transcription, Genetic/drug effects
MH  - Transplantation, Homologous
MH  - Tumor Necrosis Factor-alpha/*genetics/*metabolism
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
PST - ppublish
SO  - Bone Marrow Transplant. 1992 May;9(5):369-76.