Staphylococcal toxic shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta secretion by human peripheral blood monocytes and T lymphocytes is differentially suppressed by protein kinase inhibitors.
The signal transduction pathways by which staphylococcal toxic shock syndrome toxin 1 (TSST-1) induces tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were examined with various protein kinase inhibitors. TNF-alpha secretion by normal human monocytes and T cells in response to TSST-1 was suppressed by inhibitors of protein kinase C (H7) and tyrosine kinases (genistein). In contrast, the secretion of IL-1 beta was blocked by a cyclic AMP- and cyclic GMP-dependent kinase inhibitor (HA1004) as well as by H7 and genistein. These results suggest that the secretion of TNF-alpha and IL-1 beta may be differentially regulated by TSST-1 and that protein kinases play an important role in mediating cytokine responses to the toxin.
See
R H
RH
Department of Medicine, University of British Columbia, Vancouver, Canada.
Chow
A W
AW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology*; D019833:Genistein; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides; D009000:Monocytes / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013449:Sulfonamides; D018089:Superantigens; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D007529:Isoflavones; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D019833:Genistein; D011494:Protein Kinases