Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40

James L Slack, J. Nemunaitis, D. F. Andrews, J. W. Singer

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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-1α (IL-1α) or tumor necrosis factor-α (TNFα). 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-1α and TNFα. IL-1α induced significant and prolonged increases in steady-state mRNA levels for interleukin-6 (IL-6), interleukin-1β (IL-1β), 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-1α transcriptionally activated the genes for IL-6, GM-CSF, and IL-1β, while TNFα transcriptionally induced expression of IL-6 and IL-1β. Furthermore, mRNA for IL-6 and IL-1β was dramatically superinduced by the combination of cycloheximide and TNFα. 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-1β. In this report, we show that the expression of IL-6 and IL-1β mRIMA 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-1α- and/or TNFα-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.

Original languageEnglish (US)
Pages (from-to)2319-2327
Number of pages9
JournalBlood
Volume75
Issue number12
StatePublished - Jun 15 1990
Externally publishedYes

Fingerprint

Simian virus 40
Mesenchymal Stromal Cells
Interleukin-1
Viruses
Gene expression
Intercellular Signaling Peptides and Proteins
Bone
Cytokines
Gene Expression
Interleukin-6
Granulocytes
Macrophages
Tumor Necrosis Factor-alpha
Stromal Cells
Colony-Stimulating Factors
Genes
Cells
Cell Line
Messenger RNA
Transcriptional Activation

ASJC Scopus subject areas

  • Hematology

Cite this

Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40. / Slack, James L; Nemunaitis, J.; Andrews, D. F.; Singer, J. W.

In: Blood, Vol. 75, No. 12, 15.06.1990, p. 2319-2327.

Research output: Contribution to journalArticle

Slack, James L ; Nemunaitis, J. ; Andrews, D. F. ; Singer, J. W. / Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40. In: Blood. 1990 ; Vol. 75, No. 12. pp. 2319-2327.
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