Intracellular pathways involved in tumor necrosis factor-alpha release by human monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan are partly similar

J Infect Dis. 1996 Jan;173(1):212-8. doi: 10.1093/infdis/173.1.212.

Abstract

This study compared the effects of intracellular pathway inhibitors on tumor necrosis factor-alpha (TNF-alpha) release from human monocytes. Cells were stimulated with peptidoglycan (PG) from Staphylococcus epidermidis or with Escherichia coli lipopolysaccharide (LPS), both in the presence of 10% human serum. Of 10 substances tested, only the protein tyrosine kinase inhibitor tyrphostin AG 126 discriminated significantly between PG and LPS: TNF-alpha release induced by PG, but not by LPS, was dose-dependently suppressed. The results obtained with other modulatory substances, including different protein kinase and G protein inhibitors, suggest that calmodulin-dependent protein kinase, protein tyrosine kinase, and a cholera-toxin-sensitive G protein are involved in both PG- and LPS-induced TNF-alpha release. Further, drugs such as pentoxifylline, chloroquine, and the antioxidant apocynin similarly inhibited TNF-alpha release by PG- as well as LPS-stimulated cells.

Publication types

  • Comparative Study

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Acetophenones / pharmacology
  • Alkaloids / pharmacology
  • Antimalarials / pharmacology
  • Cell Communication / physiology*
  • Chloroquine / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / metabolism
  • Humans
  • Isoquinolines / pharmacology
  • Lipopolysaccharides / pharmacology*
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Pentoxifylline / pharmacology
  • Peptidoglycan / pharmacology*
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction / physiology*
  • Staphylococcus epidermidis
  • Staurosporine
  • Sulfonamides / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vasodilator Agents / pharmacology

Substances

  • Acetophenones
  • Alkaloids
  • Antimalarials
  • Enzyme Inhibitors
  • Isoquinolines
  • Lipopolysaccharides
  • Peptidoglycan
  • Piperazines
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • W 7
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Chloroquine
  • acetovanillone
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • GTP-Binding Proteins
  • Staurosporine
  • Pentoxifylline