Additive effects of interleukin 1 and tumour necrosis factor-alpha on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells.

Abstract

The control of haematopoietic colony‐stimulating factors (CSF) gene expression by interleukin 1 (IL‐1) and tumour necrosis factor alpha (TNF‐alpha) in cultured endothelial cells was studied by RNA hybridization and nuclear gene transcription. Both IL‐1 and TNF‐alpha induced, with somewhat different kinetics, a slow but marked accumulation of granulocyte‐macrophage (GM)‐ and granulocyte (G)‐CSF mRNAs in endothelial cells; macrophage (M)‐CSF mRNA increased more rapidly but more moderately. Simultaneous treatment with maximally stimulating concentrations of both IL‐1 and TNF‐alpha had an additive effect on the accumulation of the three mRNAs, suggesting that both mediators act via independent pathways. The mechanism of CSF mRNA accumulation in endothelial cells was explored by nuclear run‐on experiments, which showed that both IL‐1 and TNF‐alpha increase GM‐CSF, G‐CSF and M‐CSF gene transcription to varying degrees.

Dexamethasone regulation of the expression of cytokine mRNAs induced by interleukin‐1 in the astrocytoma cell line U373MG

“…We have observed that G-CSF mRNA was also induced although its level was very low (not shown), and therefore we did not study G-CSF mRNA induction further. Seelentag et al [10] have reported that IL-1 induced the expression of GM-CSF, G-CSF and M-CSF mRNAs in human endothelial cells and Yasukawa et al [17] have shown BSF-2 mRNA induction by rlL-lfl in U373MG cells. Our results showed that IL-I~' induced not only GM-CSF and G-CSF mRNAs but also those of BSF-2 and IL-ld in astrocytoma cell line.…”

“…Seelentag et al [10] have described that the induction of GM-CSF mRNA by IL-1 in human endothelial cells was not affected by dexamethasone, while Thorens et al [23] have reported that dexamethasone completely prevented GM-CSF mRNA induction by LPS. We therefore studied the effect of dexamethasone on the induction of BSF-2, GM-CSF and IL-I~' mRNAs by rIL-l~'.…”

“…Its biological activities include induction of various cytokines. IL-1 has been shown to induce the production of granulocytemacrophage colony-stimulating factor [5][6][7][8][9][10][11][12][13], granulocyte CSF (G-CSF) [9][10][11][12] and B-cell stimulatory factor-2/interleukin-6/interferon-fl2 (IFN-~2)/26-kDa protein [14][15][16][17]. Recently it has also been reported that IL-1 can induce its own synthesis [18][19][20].…”

G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome

“…There is very little information on levels of G-CSF in the lungs of healthy subjects, but alveolar macrophages recovered by BAL from healthy controls can produce G-CSF after stimulation with endotoxin [24]. The sources of G-CSF in the lungs of patients with ARDS are unknown, but G-CSF can be produced by monocytes, macrophages, endothelial cells and fibroblasts in vitro in response to stimulation by IL-1 and tumour necrosis factor-a, which are key inflammatory mediators in ARDS [25,26]. In addition, bronchial epithelial cells containing G-CSF messenger ribonucleic acid have been seen in a rat model of acute lung injury [26].…”

“…The sources of G-CSF in the lungs of patients with ARDS are unknown, but G-CSF can be produced by monocytes, macrophages, endothelial cells and fibroblasts in vitro in response to stimulation by IL-1 and tumour necrosis factor-a, which are key inflammatory mediators in ARDS [25,26]. In addition, bronchial epithelial cells containing G-CSF messenger ribonucleic acid have been seen in a rat model of acute lung injury [26]. Further studies are now needed to identify the main sources of G-CSF in the lungs of patients with ARDS and to clarify its role in pathogenesis.…”