Mechanism of stimulation by human interferon of prostaglandin synthesis in human cell lines.

  • Moreno J
  • Krishnan A
  • Swami S
 et al. 
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Abstract

Human interferon beta (IFN-beta) stimulated the synthesis of prostaglandin E (PGE) and prostaglandin F2 alpha in IFN-sensitive RSa and GM258 cell lines, but not in IFN-resistant HEC-1 cells. IFN-beta at a concentration of 1000 units/ml elicited 2- to 3-fold increases in PGE production in these cell lines. In the presence of exogenous arachidonic acid (1 microgram/ml), IFN-pretreated cells produced 5-fold more PGE compared to the cell cultures in the absence of arachidonic acid. Prednisolone, an inhibitor of phospholipase A2, at a concentration of 2 micrograms/ml inhibited the enhanced synthesis of PGE by IFN-pretreated cells. Indomethacin (4 micrograms/ml), a potent fatty acid cyclooxygenase inhibitor, also inhibited the increased synthesis of PGE. IFN stimulated the release of 14Carachidonic acid from phospholipids but did not stimulate the activity of fatty acid cyclooxygenase. These data suggest that IFN stimulates prostaglandin synthesis by promoting the release of arachidonic acid from phospholipids. Since cycloheximide and actinomycin D inhibited the stimulation of PGE synthesis, the stimulation of prostaglandin synthesis by IFN seemed to be due to de novo enzyme synthesis which catalyzes the release of fatty acid. Addition of exogenous PGE suppressed the growth of RSa and GM258 cells. Prednisolone and iodomethacin partially inhibited anti-cell growth activity of IFN, suggesting a possibility that IFN-inhibited cell growth was partly mediated by prostaglandin.

Author-supplied keywords

  • anti inflammatory agents
  • calcitriol
  • calcitriol pharmacology
  • cell growth processes
  • cell growth processes drug effects
  • cyclooxygenase 2
  • dinoprostone
  • dinoprostone biosynthesis
  • drug synergism
  • fos
  • gene expression regulation
  • genes
  • hormone dependent
  • hormone dependent drug therapy
  • hormone dependent metabolism
  • hormone dependent pathology
  • humans
  • hydroxyprostaglandin dehydrogenases
  • hydroxyprostaglandin dehydrogenases biosynthesis
  • hydroxyprostaglandin dehydrogenases genetics
  • hydroxyprostaglandin dehydrogenases metabolism
  • male
  • membrane proteins
  • messenger
  • messenger biosynthesis
  • messenger genetics
  • neoplasms
  • neoplastic
  • neoplastic drug effec
  • non steroidal
  • non steroidal pharmacol
  • prostaglandin
  • prostaglandin biosynthesis
  • prostaglandin endoperoxide synthases
  • prostaglandin endoperoxide synthases biosynthesis
  • prostaglandin endoperoxide synthases genetics
  • prostaglandin endoperoxide synthases metabolism
  • prostaglandin metabolism
  • prostaglandins
  • prostaglandins biosynthesis
  • prostatic neoplasms
  • prostatic neoplasms drug therapy
  • prostatic neoplasms genetics
  • prostatic neoplasms metabolism
  • prostatic neoplasms pathology
  • receptors
  • rna

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  • PMID: 6178505

Authors

  • Jacqueline Moreno

  • Aruna V Krishnan

  • Srilatha Swami

  • Larisa Nonn

  • Donna M Peehl

  • David Feldman

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