Dysregulated Production of Interferon-gamma, Interleukin-4 and Interleukin-6 in Early Tuberculosis Patients in Response to Antigen 85B of Mycobacterium tuberculosis

The murine myeloid leukemia cell line M1 induced by interleukin-6 (IL- 6) is a model system to study the differentiation of blast cells to mature macrophages. We have recently shown that IL-6 induces the expression of the IL-4 receptor (IL-4R) in these cells. In the present study we investigate the mechanism of action of interferon-gamma (IFN- gamma), an antagonist of IL-4 in numerous cells and a cofactor in both induction and suppression of myelopoiesis, on the expression of IL-4R. Flow cytometry shows that IFN-gamma downregulates the IL-6-induced expression of IL-4R whereas it has no such effect on the high-affinity receptors for monomeric IgG2a (Fc gamma RI). As demonstrated by Scatchard analysis, the number of IL-4R decreases by more than 50% after IFN-gamma treatment whereas the receptor affinity remains unchanged. Northern analysis shows that this decrease is paralleled by a decrease in IL-4R mRNA but not Fc gamma RI or lysozyme mRNA. Nuclear run-on analysis shows that IFN-gamma suppresses the IL-6-induced transcription of the IL-4R gene, whereas actinomycin-D chase experiments showed no change of IL-4R mRNA stability. Furthermore, the production of soluble IL-4R protein is suppressed by IFN-gamma as well. These data explain how IL-4R can be modulated by IFN-gamma in myeloid cells and are consistent with the myelosuppressive capacity of IFN- gamma.

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Matrix metalloproteinase expression by Mycobacterium tuberculosis-infected human macrophages is modulated by interferon-gamma and interleukin-4

Journal of Infection ◽

10.1016/j.jinf.2010.09.010 ◽

2010 ◽

Vol 61 (6) ◽

pp. 518-519

Author(s):

Rachel Moores ◽

Lucinda Rand ◽

Paul Elkington ◽

Jonathan Friedland

Keyword(s):

Mycobacterium Tuberculosis ◽

Matrix Metalloproteinase ◽

Interferon Gamma ◽

Interleukin 4 ◽

Human Macrophages

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Interferon-gamma antagonizes interleukin-6-induced expression of interleukin-4 receptors in murine myeloid cells by a transcriptional mechanism

Blood ◽

10.1182/blood.v82.9.2641.2641 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2641-2648 ◽

Cited By ~ 4

Author(s):

S Ruhl ◽

GM Feldman ◽

K Akahane ◽

DH Pluznik

Keyword(s):

Interferon Gamma ◽

Interleukin 6 ◽

Leukemia Cell ◽

Myeloid Cells ◽

Interleukin 4 ◽

Leukemia Cell Line ◽

Northern Analysis ◽

Scatchard Analysis ◽

Induced Expression ◽

Ifn Gamma

Abstract The murine myeloid leukemia cell line M1 induced by interleukin-6 (IL- 6) is a model system to study the differentiation of blast cells to mature macrophages. We have recently shown that IL-6 induces the expression of the IL-4 receptor (IL-4R) in these cells. In the present study we investigate the mechanism of action of interferon-gamma (IFN- gamma), an antagonist of IL-4 in numerous cells and a cofactor in both induction and suppression of myelopoiesis, on the expression of IL-4R. Flow cytometry shows that IFN-gamma downregulates the IL-6-induced expression of IL-4R whereas it has no such effect on the high-affinity receptors for monomeric IgG2a (Fc gamma RI). As demonstrated by Scatchard analysis, the number of IL-4R decreases by more than 50% after IFN-gamma treatment whereas the receptor affinity remains unchanged. Northern analysis shows that this decrease is paralleled by a decrease in IL-4R mRNA but not Fc gamma RI or lysozyme mRNA. Nuclear run-on analysis shows that IFN-gamma suppresses the IL-6-induced transcription of the IL-4R gene, whereas actinomycin-D chase experiments showed no change of IL-4R mRNA stability. Furthermore, the production of soluble IL-4R protein is suppressed by IFN-gamma as well. These data explain how IL-4R can be modulated by IFN-gamma in myeloid cells and are consistent with the myelosuppressive capacity of IFN- gamma.

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