Early activation events induced by the staphylococcal superantigen toxic shock syndrome toxin-1 in human peripheral blood monocytes.
Staphylococcal exotoxins (SE) bind to MHC class II molecules and induce the production of IL-1 beta and TNF-alpha in human monocytic cells. Here we show that stimulation of peripheral blood monocytes with toxic shock syndrome toxin-1 (TSST-1) induced rapid increase in tyrosine phosphorylation of cytosolic protein substrates, accumulation of inositol phosphates, and de novo tyrosine phosphorylation of the PLC-gamma 1 isozyme. Accumulation of inositol phosphates was inhibited by preincubation of cells with inhibitors of protein tyrosine kinases (PTK). Stimulation of monocytes with TSST-1 furthermore led to activation of protein kinase C (PKC). PTK and PKC activation plays a role in the induction of monokine gene transcription by SE because inhibitors of PTK and PKC reduced TSST-1-stimulated IL-1 beta and TNF-alpha gene expression. We therefore propose a model in which the induction of monokine gene transcription by TSST-1 in monocytes necessitates activation of tyrosine kinase(s) and of PKC, the latter probably by way of PLC-gamma 1.
Trede
N S
NS
Division of Immunology, Children's Hospital, Boston, Massachusetts.
Morio
T
T
Scholl
P R
PR
Geha
R S
RS
Chatila
T
T
D001427:Bacterial Toxins; D002451:Cell Compartmentation / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D009000:Monocytes / Q000276:immunology*; D015846:Monokines / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; D007295:Inositol Phosphates; D007375:Interleukin-1; D015846:Monokines; D010750:Phosphoproteins; D012333:RNA, Messenger; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases