Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor.

Broudy, Virginia C.; Kaushansky, Kenneth; Segal, Gerald M.; Harlan, John M.; Adamson, John W.

doi:10.1073/pnas.83.19.7467

Cited by 359 publications

(167 citation statements)

References 36 publications

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“…[37][38][39][40][41][42][43][44][45][46][47] The relationship between the production of these cytokines and the functional ability of EC to support hematopoiesis may help in understanding the role played by these cells in the ontogeny of the hematopoietic system as EC are intimately associated with embryonic hematopoiesis and may be involved in the development of embryonic progenitors. 52,53 EC are also part of the bone marrow stromal microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

et al. 1998

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Section: Discussionmentioning

confidence: 99%

“…[37][38][39][40][41][42][43][44][45][46][47] The functional importance of this production remains to be fully appreciated. As a direct relevant application, EC may for instance offer an improved alternative to unfractionated stroma cells as a source of feeder cells in bioreactors devised for ex vivo expansion of hematopoietic progenitors.…”

Section: Introductionmentioning

confidence: 99%

Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

et al. 1998

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“…So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6], leukemia inhibitory factor (LIF) [7] and IL-6 [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] …”

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confidence: 99%

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche. We have previously shown that human endothelial cell (EC) supernatants can induce the proliferation of hematopoietic progenitor cells (HPCs), especially after stimulation with IL-1b. To identify new potential growth factors, we compared the expression profile of IL-1b-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46 000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated multiple upregulated genes encoding extracellular proteins with a cell-cell signaling function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1-3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors. Keywords: Endothelial cells . Hematopoietic stem cells . Molecular genetics Supporting Information available online IntroductionEndothelial cells (ECs) have been shown to support the proliferation of hematopoietic CD34 1 progenitor cells by the constitutive production of cytokines [1,2]. In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] 1774inhibitory factor (LIF) [7] and 9]. Beyond the known cytokine scenario, ECs synthesize multiple other proteins [10], i.e. chemokines of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown.Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes [11][12][13][14][15]. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades [16], specify the role of inflammatory stimuli in neutrophil transmigration [17] and identify the effects of biochemical forces [18]. Microarrays of cultured HPCs also defined detrimental components of engineered extracellular matrices [19]. To use microarrays of feeder cells for the identification of new hematopoietic growth factors is another aspect. Choong e...

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“…Second passage HUVEC were grown to confluence using culture :onditions previously described [25] in duplicate gelatin-coated 96 well )lares. After stimulation with cytokines, the supernatants were removed ?ore each plate and assayed for GM-CSF by ELISA activity as previmsly described [26].…”

Section: '1 Elisa Of Huvecmentioning

confidence: 99%

Interleukin‐4 induces endothelial vascular cell adhesion molecule‐1 (VCAM‐1) by an NF‐κb‐independent mechanism

McCarty¹,

Yee²,

Deisher³

et al. 1995

FEBS Letters

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While all features of the inflammatory response induced by IL-I are not observed following IL-4 stimulation, suboptimal concentrations both cytokines result in synergistic VCAM-1 expression in HUVEC. We have shown that, while IL-1 stimulated HUVEC express GM-CSF, tissue factor and VCAM-1, only VCAM-1 is detectable after exposure to IL-4. While kB was found essential for both basal and IL-l-mediated activity of VCAM-I, IL-4 induction was kB-independent. Inducible kBbinding proteins were identified in IL-I-, but not IL-4-stimulated nuclear extracts. Our results indicate that IL-4 exerts its transcriptional effects on the VCAM-I gene through element(s) which do not require kB.

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Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor.

Abstract: Tumor necrosis factor type a (TNF-a) is produced by monocytes and has been purified, sequenced, and cloned from the HL-60 cell line.

Cited by 359 publications

References 36 publications

Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

Endothelial cell support of hematopoiesis is differentially altered by IL-1 and glucocorticoids

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Interleukin‐4 induces endothelial vascular cell adhesion molecule‐1 (VCAM‐1) by an NF‐κb‐independent mechanism

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