LIF mRNA expression is transcriptionally regulated in murine bone marrow stromal cells

H. Günter Derigs, H. Boswell

Research output: Contribution to journalArticle

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Abstract

Recent evidence has established an important role for leukemia inhibitory factor (LIF) as hematopoietically active cytokine. The present study utilized two different murine bone marrow stromal cell lines, +/+ -1.LDA11 and MBA-13, to define regulatory mechanisms of LIF messenger RNA (mRNA) induction. LIF mRNA was not detected in uninduced stromal cells under serum-free conditions. Incubation with interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) or the cAMP analogue 8-bromoadenosine 3′:5′-monophosphate (8BrcAMP) resulted in weakly induced LIF mRNA. Coincubation of combinations of these stimuli increased LIF mRNA expression additively. LIF mRNA stability, even after stimulation, was low with a half-life of about 30 min, suggesting a functional role for known AU-rich motifs in the 3′ untranslated LIF mRNA region in mediating this instability. This possibility was further supported by the ability of cycloheximide to increase mRNA levels without affecting transcription. Transcriptional activation was found to be the main mechanism leading to LIF mRNA expression by IL-1, by TNF-α, and by 8BrcAMP. These stimuli appeared to act additively in this regard, suggesting involvement of distinct transcription factors. Induction of transcription was detected 45 min post-stimulation and showed peak levels at 90 min. Kinetics of LIF transcriptional activation showed similarity with the kinetics of the transcription factors, jun-B and c-fos, suggesting a possible role for these proteins or other early response genes in events leading to LIF expression.

Original languageEnglish
Pages (from-to)630-634
Number of pages5
JournalLeukemia
Volume7
Issue number4
StatePublished - Apr 1993

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Leukemia Inhibitory Factor
Mesenchymal Stromal Cells
Messenger RNA
Interleukin-1
Transcriptional Activation
Transcription Factors
Tumor Necrosis Factor-alpha
RNA Stability
Cycloheximide
Stromal Cells
Half-Life
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

LIF mRNA expression is transcriptionally regulated in murine bone marrow stromal cells. / Derigs, H. Günter; Boswell, H.

In: Leukemia, Vol. 7, No. 4, 04.1993, p. 630-634.

Research output: Contribution to journalArticle

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