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Titolo:
Regulation of hematopoietic growth factor production by genetically modified human bone marrow stromal cells expressing interleukin-1 beta antisense RNA
Autore:
Hartwig, UF; Keller, U; Huber, C; Peschel, C;
Indirizzi:
Univ Mainz, Dept Med 3, Mainz, Germany Univ Mainz Mainz GermanyUniv Mainz, Dept Med 3, Mainz, Germany Tech Univ Munich, Dept Med 3, D-8000 Munich, Germany Tech Univ Munich Munich Germany D-8000 ept Med 3, D-8000 Munich, Germany
Titolo Testata:
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
fascicolo: 10, volume: 21, anno: 2001,
pagine: 851 - 860
SICI:
1079-9907(200110)21:10<851:ROHGFP>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTORS; CHRONIC MYELOGENOUS LEUKEMIA; GENE-EXPRESSION; GRANULOCYTE-MACROPHAGE; RECEPTOR ANTAGONIST; PROGENITOR CELLS; MESSENGER-RNA; CULTURES; INVITRO; LINES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Peschel, C Univ Mainz, Dept Med 3, Mainz, Germany Univ Mainz Mainz Germany v Mainz, Dept Med 3, Mainz, Germany
Citazione:
U.F. Hartwig et al., "Regulation of hematopoietic growth factor production by genetically modified human bone marrow stromal cells expressing interleukin-1 beta antisense RNA", J INTERF CY, 21(10), 2001, pp. 851-860

Abstract

Interleukin-1 (IL-1) plays a major role in the regulation of bone marrow stromal cell function and hematopoiesis. It is known to induce secretion of the hematopoietic growth factors granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), IL-6, and IL-8 as well as IL-1 itself in stromal cells. We investigated the role of IL-1 beta -mediated growth factor production in the human stromal cell line L88/5. Using liposome-mediated DNA transfer, two stromal cell transfectants that constitutively express IL-1 beta antisense (AS) RNA were generated. Expression of IL-1 beta AS RNA and IL-1 beta RNA was determined by RT-PCR. The stromal cell transfectants were strongly impaired in their endogenous IL-1 beta production, andthis effect was present even when strong IL-1 beta inducers, such as IL-1 alpha and tumor necrosis factor-alpha (TNF-alpha), were used. Reduced endogenous IL-1 beta levels had no effect on the constitutive production of IL-6, IL-8, and GM-CSF measured by ELISA. In contrast to lipopolysaccharide (LPS) stimulation, IL-1 alpha -mediated stimulation of GM-CSF production was significantly reduced in AS transfectants. TNF-alpha induced GM-CSF production was also reduced. IL-6 and IL-8 production was increased in transfectants, suggesting a negative regulatory role of IL-1 beta in L88/5. This new approach using AS technology to specifically target constitutive RNA expression will allow further characterization of the bone marrow cytokine network in normal and malignant hematopoiesis.

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Documento generato il 05/04/20 alle ore 07:09:35