Lipopolysaccharide (LPS) is a potent inducer of macrophage inflammatory protein-1 alpha (MIP-1 alpha) production in human polymorphonuclear leukocytes (PMN), and it was recently shown that Interferon- gamma (IFN gamma) transiently inhibits MIP-1 alpha mRNA accumulation in LPS-stimulated PMN. To elucidate the molecular basis of the regulation of MIP-1 alpha gene expression in PMN, we investigated the effects of LPS and IFN gamma at both transcriptional and post-transcriptional levels. Nuclear run-on analysis revealed that LPS increases the transcription rate of the MIP-1 alpha gene, and that IFN gamma markedly inhibits the rate of MIP-1 alpha gene transcription in LPS-activated neutrophils. IFN gamma did not affect MIP-1 alpha mRNA stability in LPS-treated PMN, indicating that the cytokine does not regulate the LPS-induced MIP-1 alpha gene expression through post-transcriptional events. These results demonstrate that human neutrophils can actively transcribe the MIP-1 alpha gene, and that transcriptional i

Interferon-gamma inhibits the lipopolysaccharide-induced macrophage inflammatory protein-1 alpha gene transcription in human neutrophils

CASSATELLA, Marco Antonio
1996-01-01

Abstract

Lipopolysaccharide (LPS) is a potent inducer of macrophage inflammatory protein-1 alpha (MIP-1 alpha) production in human polymorphonuclear leukocytes (PMN), and it was recently shown that Interferon- gamma (IFN gamma) transiently inhibits MIP-1 alpha mRNA accumulation in LPS-stimulated PMN. To elucidate the molecular basis of the regulation of MIP-1 alpha gene expression in PMN, we investigated the effects of LPS and IFN gamma at both transcriptional and post-transcriptional levels. Nuclear run-on analysis revealed that LPS increases the transcription rate of the MIP-1 alpha gene, and that IFN gamma markedly inhibits the rate of MIP-1 alpha gene transcription in LPS-activated neutrophils. IFN gamma did not affect MIP-1 alpha mRNA stability in LPS-treated PMN, indicating that the cytokine does not regulate the LPS-induced MIP-1 alpha gene expression through post-transcriptional events. These results demonstrate that human neutrophils can actively transcribe the MIP-1 alpha gene, and that transcriptional i
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/512
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