PMID- 1693528
OWN - NLM
STAT- MEDLINE
DCOM- 19900718
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 75
IP  - 12
DP  - 1990 Jun 15
TI  - Regulation of cytokine and growth factor gene expression in human bone marrow 
      stromal cells transformed with simian virus 40.
PG  - 2319-27
AB  - Marrow stromal cells are thought to regulate hematopoiesis by producing 
      colony-stimulating factors (CSFs) and other cytokines, either constitutively or 
      in response to mediators such as interleukin-1 alpha (IL-1 alpha) or tumor 
      necrosis factor-alpha (TNF alpha). The mechanisms by which these inflammatory 
      cytokines induce CSF expression in stromal cells are not fully defined. In this 
      study, we used human marrow stromal cells transformed by simian virus 40 
      (SV-MSCs) to study growth factor and cytokine gene regulation in response to IL-1 
      alpha and TNF alpha. IL-1 alpha induced significant and prolonged increases in 
      steady-state mRNA levels for interleukin-6 (IL-6), interleukin-1 beta (IL-1 
      beta), granulocyte-macrophage CSF (GM-CSF), and, to a lesser extent, 
      granulocyte-CSF (G-CSF); this induction was not dependent on new protein 
      synthesis. Nuclear run-on analyses showed that IL-1 alpha transcriptionally 
      activated the genes for IL-6, GM-CSF, and IL-1 beta, while TNF alpha 
      transcriptionally induced expression of IL-6 and IL-1 beta. Furthermore, mRNA for 
      IL-6 and IL-1 beta was dramatically superinduced by the combination of 
      cycloheximide and TNF alpha. When SV-MSCs were cultured in semisolid medium, they 
      formed colonies of blast-like cells that, when replated on plastic, resumed 
      adherent growth. These "colony-derived" cell lines, unlike the parental SV-MSCs 
      from which they were derived, constitutively expressed colony-stimulating 
      activity and mRNA for GM-CSF, G-CSF, IL-6, and IL-1 beta. In this report, we show 
      that the expression of IL-6 and IL-1 beta mRNA in the colony-derived cell lines 
      was due, at least in part, to constitutive transcriptional activation of these 
      genes (similar to the findings in IL-1 alpha- and/or TNF alpha-stimulated 
      parental SV-MSCs). However, in contrast to the transcriptional activation of the 
      GM-CSF gene seen in cytokine-induced parental SV-MSCs, GM-CSF transcripts 
      accumulated in the colony-derived cell lines by a posttranscriptional mechanism.
FAU - Slack, J L
AU  - Slack JL
AD  - Department of Medicine, University of Washington, Seattle.
FAU - Nemunaitis, J
AU  - Nemunaitis J
FAU - Andrews, D F 3rd
AU  - Andrews DF 3rd
FAU - Singer, J W
AU  - Singer JW
LA  - eng
GR  - CA 10333/CA/NCI NIH HHS/United States
GR  - CA 18029/CA/NCI NIH HHS/United States
GR  - HL31782/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Biological Factors)
RN  - 0 (Colony-Stimulating Factors)
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 98600C0908 (Cycloheximide)
SB  - IM
MH  - Biological Factors/*genetics
MH  - Blotting, Northern
MH  - *Bone Marrow Cells
MH  - Cell Line
MH  - Cell Transformation, Viral
MH  - Colony-Stimulating Factors/genetics
MH  - Cycloheximide/pharmacology
MH  - Cytokines
MH  - *Gene Expression Regulation/drug effects
MH  - Granulocyte Colony-Stimulating Factor
MH  - Granulocyte-Macrophage Colony-Stimulating Factor
MH  - Growth Substances/genetics/*physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-1/genetics/pharmacology
MH  - Interleukin-6/genetics
MH  - Simian virus 40/genetics
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1990/06/15 00:00
MHDA- 1990/06/15 00:01
CRDT- 1990/06/15 00:00
PHST- 1990/06/15 00:00 [pubmed]
PHST- 1990/06/15 00:01 [medline]
PHST- 1990/06/15 00:00 [entrez]
AID - S0006-4971(20)83129-2 [pii]
PST - ppublish
SO  - Blood. 1990 Jun 15;75(12):2319-27.