Early Activation Events Induced by the Staphylococcal Superantigen Toxic Shock Syndrome Toxin-1 in Human Peripheral Blood Monocytes

Abstract

Staphylococcal exotoxins (SE) bind to MHC class II molecules and induce the production of IL-1β and TNF-α 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-γ1 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-1β and TNF-α 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-γ1.