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

Abstract

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.