Intracellular pathways involved in tumor necrosis factor-alpha release by human monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan are partly similar.
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.
Eijkman-Winkler Institute for Medical Microbiology, Utrecht University, Utrecht, Netherlands.
E
E
Mattsson
H
H
Van Dijk
K
K
Van Kessel
J
J
Verhoef
A
A
Fleer
J
J
Rollof
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000098:Acetophenones / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D013212:Staphylococcus epidermidis; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D000098:Acetophenones; D000470:Alkaloids; D000962:Antimalarials; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002738:Chloroquine; C056165:acetovanillone; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D019311:Staurosporine; D010431:Pentoxifylline