Spontaneous and Inducible Production of Leukaemia Inhibitory Factor by Human Bone Marrow Stromal Cells

Lorgeot, Valérie; Rougier, F.; Fixe, P.; Cornu, Élisabeth; Perreten, Vincent; Denizot, Yves

doi:10.1006/cyto.1997.0225

Cited by 24 publications

(8 citation statements)

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“…GM-CSF and G-CSF mRNAs were clearly induced in two of three and three of four experiments respectively. As suggested by observations made with other stromal cell lines [44,45], these studies demonstrate a potent innate inflammatory cytokine response against bacterial LPS. It should be noted that these studies do not exclude possible LIF or other cytokines at other time points.…”

Section: Resultssupporting

confidence: 75%

Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

et al. 2003

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BackgroundBone marrow stromal cells produce cytokines required for the normal growth and development of all eight hematopoietic cell lineages. Aberrant cytokine production by stromal cells contributes to blood cell dyscrasias. Consequently, factors that alter stromal cell cytokine production may significantly compromise the development of normal blood cells. We have shown that environmental chemicals, such as aromatic hydrocarbon receptor (AhR) agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell function. Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to alter stromal cell cytokine responses.MethodsBone marrow stromal cells were treated with AhR agonists and bacterial lipopolysaccharide (LPS) to mimic innate inflammatory cytokine responses and to study the effects of AhR ligands on those responses. Steady state cytokine RNA levels were screened by RNAse protection assays (RPA) and quantified by real-time PCR. Cytokine (IL-6) protein production was measured by ELISA. NF-κB EMSAs were used to study IL-6 transcriptional regulation.ResultsRPAs indicated that AhR+ bone marrow stromal cells consistently up-regulated genes encoding IL-6 and LIF in response to LPS, presumably through activation of Toll-like receptor 4. Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was reflected in a profound down-regulation of IL-6 protein induction, with DMBA and TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-κB binding to IL-6 promoter sequences, an event known to induce IL-6 transcription, indicated a significant decrease in the LPS-mediated induction of DNA-binding RelA/p50 and c-Rel/p50 heterodimers in the presence of DMBA.ConclusionsCommon environmental AhR agonists can suppress the response to bacterial lipopolysaccharide, a model for innate inflammatory responses, through down-regulation of IL-6, a cytokine critical to the growth of several hematopoietic cell subsets, including early B cells. This suppression occurs at least at the level of IL-6 gene transcription and may be regulated by NF-κB.

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Section: Resultssupporting

confidence: 75%

Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

et al. 2003

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“…Indeed several clinical trials evidenced that injection of MSC to Bone Marrow (BM) allografted patients reduced their graft versus host disease by improving the donor T cells immune tolerance [130]. Interestingly, LIF is produced by human BMMSC [131] and its overexpression and depletion in mouse models led to immune disturbances [132]. Recently, it was suggested that the MSC-induced immune tolerance is due to their production of LIF [133].…”

Section: Lif In Stem Cellsmentioning

confidence: 99%

LIF-Dependent Signaling: New Pieces in the Lego

Mathieu

Saucourt

Mournetas

et al. 2011

Stem Cell Rev and Rep

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LIF, a member of the IL6 family of cytokine, displays pleiotropic effects on various cell types and organs. Its critical role in stem cell models (e.g.: murine ES, human mesenchymal cells) and its essential non redundant function during the implantation process of embryos, in eutherian mammals, put this cytokine at the core of many studies aiming to understand its mechanisms of action, which could benefit to medical applications. In addition, its conservation upon evolution raised the challenging question concerning the function of LIF in species in which there is no implantation. We present the recent knowledge about the established and potential functions of LIF in different stem cell models, (embryonic, hematopoietic, mesenchymal, muscle, neural stem cells and iPSC). We will also discuss EVO-DEVO aspects of this multifaceted cytokine.

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“…In the present study, we examined the signal transduction pathways in serum‐induced LIF and IL‐6 production by bone marrow stromal cell line, HS‐5. Bone marrow stromal cells were reported to produce haematopoietic cytokines in response to lipopolysaccharide or inflammatory mediators such as IL‐1α and TNF‐α (Fibbe et al ., 1988; Lorgeot et al ., 1997; Rougier et al ., 1998). However, in the absence of such inflammatory stimuli, many kinds of haematopoietic cytokines are secreted for steady‐state haematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies provide evidence that these signal transduction cascades mediate the production of cytokines in various types of cells (Carter et al ., 1999; Hashimoto et al ., 2000; Marin et al ., 2001). Human bone marrow stromal cells were reported to product LIF and IL‐6 spontaneously, in response to serum and monocyte‐derived cytokines such as interleukin‐1α (IL‐1α) and tumour necrosis factor‐α (TNF‐α) (Lorgeot et al ., 1997; Rougier et al ., 1998). However, the intracellular signal that regulates cytokine expression in bone marrow stromal cells has not been determined.…”

Section: Introductionmentioning

confidence: 99%

Role of mitogen‐activated protein kinase family in serum‐induced leukaemia inhibitory factor and interleukin‐6 secretion by bone marrow stromal cells

Nakao

Kim

Ohta

et al. 2002

British J Pharmacology

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1 In the haematopoietic microenvironment, bone marrow stromal cells play an important role in regulating haematopoiesis by expressing various cytokines, including leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6). However, the intracellular signal that regulates cytokine secretion in bone marrow stromal cells has not been determined. The aim of this study was to evaluate the role of mitogen-activated protein kinase (MAPK) family in serum-induced secretion of LIF and IL-6 by bone marrow stromal cells. 2 Transformed human bone marrow stromal cells (HS-5) were stimulated with foetal calf serum (FCS) to produce LIF and IL-6. FCS also induced activation of extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun NH 2 -terminal kinase (JNK). 3 Both PD98059 (MAPK/ERK kinase inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated FCS-induced LIF protein production and gene expression. SB203580 decreased IL-6 production and gene expression, but PD98059 had no e ect on IL-6 production and gene expression. 4 Expression of a dominant-negative mutant form of JNK1 that blocked FCS-induced JNK activity had no e ect on protein production and gene expression of these cytokines. 5 These ®ndings demonstrate that both ERK and p38 MAPK are involved in FCS-induced LIF secretion, whereas only p38 MAPK is important for IL-6 secretion, and that FCS-induced activation of JNK has no e ect on the production of LIF and IL-6. We conclude that, in spite of their similar biological e ects, they are di erentially regulated at the level of MAPK activity in bone marrow stromal cells. British Journal of Pharmacology (2002) 136, 975 ± 984

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Spontaneous and Inducible Production of Leukaemia Inhibitory Factor by Human Bone Marrow Stromal Cells

Cited by 24 publications

References 0 publications

Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

LIF-Dependent Signaling: New Pieces in the Lego

Role of mitogen‐activated protein kinase family in serum‐induced leukaemia inhibitory factor and interleukin‐6 secretion by bone marrow stromal cells

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