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

Immunol Lett. 1996 Jan;49(1-2):79-82. doi: 10.1016/0165-2478(95)02484-0.

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 inhibition is the mechanism whereby IFN gamma inhibits MIP-1 alpha gene expression in PMN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL4
  • Growth Inhibitors / pharmacology*
  • Humans
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Macrophage Inflammatory Proteins / antagonists & inhibitors*
  • Macrophage Inflammatory Proteins / genetics*
  • Neutrophils / metabolism*
  • RNA, Messenger / analysis
  • Transcription, Genetic / drug effects*
  • Transcription, Genetic / immunology

Substances

  • Chemokine CCL4
  • Growth Inhibitors
  • Lipopolysaccharides
  • Macrophage Inflammatory Proteins
  • RNA, Messenger
  • Interferon-gamma