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We studied the effect of the stroma-derived cytokine interleukin-7 (IL-7) on the expression of IL-4 in human T cells at mRNA and protein level. The results demonstrate that IL-7 did not induce IL-4 mRNA in resting T cells. However, concanavalin A (con A)-induced IL-4 mRNA. expression was enhanced by costimulation with con A plus IL-7. Nuclear run-on analysis revealed that IL-7 did not affect the transcription rate of the IL-4 gene. The half-life of con A-induced IL-4 transcripts, however, was increased upon con A plus IL-7 treatment, indicating that the effect of IL-7 is mediated at posttranscriptional level. In accordance with the mRNA results, IL-4 protein was not detected in supernatants of unstimulated T cells or T cells exposed to IL-7. In contrast, IL-7 augmented the con A-induced secretion of IL-4 protein significantly. In addition, it was noticed that anti-IL-1 beta and anti-tumor necrosis factor-a (anti-TNF-alpha) did not abolish the effect of IL-7 on the con A-induced IL-4 secretion, indicating that the IL-7 effect is not mediated by the release of these cytokines. These results indicate that a stroma-derived factor can affect IL-4 expression in activated human T cells.

We studied the effect of the stroma-derived cytokine interleukin-7 (IL-7) on the expression of IL-4 in human T cells at mRNA and protein level. The results demonstrate that IL-7 did not induce IL-4 mRNA in resting T cells. However, concanavalin A (con A)-induced IL-4 mRNA. expression was enhanced by costimulation with con A plus IL-7. Nuclear run-on analysis revealed that IL-7 did not affect the transcription rate of the IL-4 gene. The half-life of con A-induced IL-4 transcripts, however, was increased upon con A plus IL-7 treatment, indicating that the effect of IL-7 is mediated at posttranscriptional level. In accordance with the mRNA results, IL-4 protein was not detected in supernatants of unstimulated T cells or T cells exposed to IL-7. In contrast, IL-7 augmented the con A-induced secretion of IL-4 protein significantly. In addition, it was noticed that anti-IL-1 beta and anti-tumor necrosis factor-a (anti-TNF-alpha) did not abolish the effect of IL-7 on the con A-induced IL-4 secretion, indicating that the IL-7 effect is not mediated by the release of these cytokines.These results indicate that a stroma-derived factor can affect IL-4 expression in activated human T cells.

Human adherent monocytes were studied with regard to the expression of granulocyte colony-stimulating factor (G-CSF) at mRNA and protein levels in response to lipopolysaccharide (LPS) and gamma-interferon (IFN-gamma) stimulation. Monocytes did not express G-CSF transcripts in response to IFN-gamma treatment. In contrast, monocytes exposed to IFN-gamma plus LPS showed a dose-dependent increase in G-CSF mRNA accumulation and protein secretion compared to LPS-stimulated monocytes. The augmented G-CSF mRNA expression in response to IFN-gamma plus LPS was the result of a slight increase in the G-CSF transcription rate (2.2-fold) and a more than 6-fold increase in the G-CSF mRNA half-life (20 minutes vs. > 120 minutes).In addition, it was shown that the effects of IFN-gamma on LPS-induced G-CSF protein secretion could be mimicked by the calcium ionophore A23187, suggesting that the Ca2+-dependent pathway might be triggered after binding of the ligand to the receptor. Finally, it was observed that the potentiating effects of IFN-gamma on LPS-induced G-CSE: secretion could be blocked by interleukin-4 (IL4). These data indicate that two cytokines produced by activated T cells have opposite effects on G-CSF production by human activated monocytes.

Human adherent monocytes were studied with regard to the expression of granulocyte colony-stimulating factor (G-CSF) at mRNA and protein levels in response to lipopolysaccharide (LPS) and gamma-interferon (IFN-gamma) stimulation. Monocytes did not express G-CSF transcripts in response to IFN-gamma treatment. In contrast, monocytes exposed to IFN-gamma plus LPS showed a dose-dependent increase in G-CSF mRNA accumulation and protein secretion compared to LPS-stimulated monocytes. The augmented G-CSF mRNA expression in response to IFN-gamma plus LPS was the result of a slight increase in the G-CSF transcription rate (2.2-fold) and a more than 6-fold increase in the G-CSF mRNA half-life (20 minutes vs. > 120 minutes). In addition, it was shown that the effects of IFN-gamma on LPS-induced G-CSF protein secretion could be mimicked by the calcium ionophore A23187, suggesting that the Ca2+-dependent pathway might be triggered after binding of the ligand to the receptor. Finally, it was observed that the potentiating effects of IFN-gamma on LPS-induced G-CSE: secretion could be blocked by interleukin-4 (IL4). These data indicate that two cytokines produced by activated T cells have opposite effects on G-CSF production by human activated monocytes.