Role of caspase in CD80 expression of superantigen-stimulated monocytes

Int J Mol Med. 2004 Aug;14(2):241-6.

Abstract

In this study, we demonstrated evidence for the induction of CD80+ monocytes by staphylococcal enterotoxin B (SEB) via caspase actions. Pre-treatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB, resulted in a significant reduction in the percentage of SEB- and interferon-gamma (IFN-gamma) (produced by SEB) -induced CD80+ monocytes. SEB and IFN-gamma activated NF-kappaB, which was inhibited by PDTC. SEB induced the activation of caspase-3 and -8, and pre-treatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis. Treating with z-VAD-fmk resulted in a reduction of the generation of CD80+ monocytes. These results indicated that CD80 driven by NF-kappaB is regulated by the enzymatic actions of caspases, which allows monocytes to participate in massive T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antibodies, Monoclonal / chemistry
  • Apoptosis
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / chemistry
  • Caspase 3
  • Caspase 8
  • Caspases / metabolism
  • Caspases / physiology*
  • Cells, Cultured
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Enterotoxins / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Middle Aged
  • Monocytes / metabolism*
  • NF-kappa B / metabolism
  • Pyrrolidines / pharmacology
  • RNA / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superantigens / metabolism*
  • T-Lymphocytes / metabolism
  • Thiocarbamates / pharmacology
  • Up-Regulation

Substances

  • Amino Acid Chloromethyl Ketones
  • Antibodies, Monoclonal
  • B7-1 Antigen
  • DNA, Complementary
  • Enterotoxins
  • Enzyme Inhibitors
  • NF-kappa B
  • Pyrrolidines
  • Superantigens
  • Thiocarbamates
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • pyrrolidine dithiocarbamic acid
  • enterotoxin B, staphylococcal
  • RNA
  • Interferon-gamma
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Caspases