Activator protein-1 (AP-1) is stimulated by microbial superantigens in human monocytic cells.
Microbial superantigens bind to major histocompatibility complex (MHC) class II molecules and activate gene transcription in monocytes. In search of transcription factors that potentially mediate the effects of superantigens at the nuclear level, we examined the capacity of staphylococcal superantigens to stimulate the activity of the transcriptional promoter factor activator protein-1 (AP-1). Electrophoretic mobility shift assays showed an increase in nuclear proteins that bound to the consensus AP-1 motif within 5 min following the stimulation of the monocytic cell line THP-1 with toxic shock syndrome toxin-1 (TSST-1) or staphylococcal endotoxin A. We show that mRNA levels for the subunits that compose AP-1, the protooncogenes c-fos and c-jun, are upregulated by stimulation of THP-1 cells with TSST-1. The activated AP-1 complexes were functional, as evidenced by the capacity of TSST-1 to stimulate the expression of an AP-1-driven reporter gene construct transfected into THP-1 cells. These results establish that the engagement of MHC class II molecules by superantigens increases the activity of functional AP-1 complexes and that this may proceed in part by transcriptional activation of c-fos and c-jun protooncogenes.
Trede
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NS
Division of Immunology, Children's Hospital, Boston, MA 02115.
Chatila
T
T
Geha
R S
RS
D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004731:Endotoxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D013211:Staphylococcus aureus; D018089:Superantigens; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016755:Proto-Oncogene Proteins c-jun; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; D003513:Cycloheximide