STAPHYLOCOCCAL TOXINS AND PROTEIN-A DIFFERENTIALLY INDUCE CYTOTOXICITY AND RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA FROM HUMAN KERATINOCYTES

It has been proposed that toxins and other bacterial protein products of Staphylococcus aureus can act as triggers or persistence factors in several inflammatory skin diseases. In this study, we examined the S. aureus isolates from the skin of patients with atopic dermatitis and psoriasis, We found that the bacterial isolates from these patients ex hibited either characteristic superantigenic toxins or thermolabile to xins believed to be staphylococcal alpha-toxin. All of these staphyloc occal strains also secreted extracellular staphylococcal protein A. We found significant differences in the action of these toxins on human keratinocytes and keratinocyte cell lines. The superantigenic toxins t oxic shock syndrome toxin-1, staphylococcal enterotoxins A and B, and exfoliative toxin-A, as well as staphylococcal protein A, did not indu ce significant cytotoxic damage in the keratinocyte cell line HaCaT, w hereas the staphylococcal alpha-toxin produced profound cytotoxicity. Keratinocyte cytotoxicity induced by staphylococcal alpha-toxin was ti me and concentration dependent and demonstrated the morphologic and fu nctional characteristics of necrosis, not apoptosis. Addition of alpha -toxin to keratinocytes simultaneously induced cell lysis and tumor ne crosis factor-alpha release into the medium within 30 min; apparently, it was constitutive tumor necrosis factor-alpha. On the other hand, s uperantigenic toxins and, in particular, protein A showed stimulation of tumor necrosis factor-alpha secretion in keratinocytes and release of this cytokine after 6-12 h of incubation. Thus, staphylococcal prot ein A, alpha-toxin, and superantigenic toxins found in S. aurueus isol ates from patients with psoriasis and atopic dermatitis can produce di rect pro-inflammatory effects on keratinocytes through the release of tumor necrosis factor-alpha. We propose that these effects may be rele vant to the induction and persistence of lesions in these two diseases .