Production of Tumor Necrosis Factor Alpha in Human T Lymphocytes by Staphylococcal Enterotoxin B Correlates with Toxin-Induced Proliferation and Is Regulated through Protein Kinase C
Abstract
The superantigen staphylococcal enterotoxin B (SEB) simultaneously binds both the major histocompatibility complex (MHC) class II receptor on monocytes and the T-cell receptor (TCR) on T lymphocytes, resulting in a range of cell responses including induction of tumor necrosis factor alpha (TNF-alpha). In this study, we have used mixed cultures of human peripheral blood monocytes and lymphocytes to investigate biochemical events controlling SEB induction of TNF-alpha. TNF-alpha production induced by SEB in mixed cultures is more closely associated with T cells than with monocytes: (i) a TCR-binding-site mutant of SEB (N23F) is less active in TNF-a induction than an MHC class II receptor-binding-site mutant (F44R), and (ii) flow cytometric analysis indicated that SEB induced TNF-a production in T cells but not in monocytes. Pretreatment of cells with inhibitors of signal transduction pathways was employed to further define events in SEB-induced TNF-a production. Neither protein kinase A inhibitors nor two protein tyrosine kinase inhibitors altered SEB-induced TNF-a production. In contrast, SEB induced protein kinase C (PKC) translocation, and pretreatment of cultures with inhibitors of PKC blocked TNF-a induction. Alteration of levels of diacylglycerol (DAG), an activator of PKC, by treatment with inhibitors of phospholipase C or DAG kinase also altered SEB-induced TNF-alpha production. These data suggest that PKC activation plays a critical role in SEB-induced TNF%-a production in human T cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1999
- Accession Number
- ADA372551
Entities
People
- David C. Yang
- Marti Jett
- Roger Neill
- Zhengyin Yan
Organizations
- Georgetown University