Inhibition of Shiga toxin-induced tumor necrosis factor-alpha production and gene expression in human monocytic cells by CV6209

Life Sci. 2001 Mar 9;68(16):1931-7. doi: 10.1016/s0024-3205(01)00979-1.

Abstract

Cytokines, in particular TNF-alpha, appear to be necessary to develop the pathological process of Shiga toxin-producing Escherichia coli (STEC) infection. In this study, we investigated whether CV6209, a PAF antagonist, could modulate Shiga toxin (Stx)-induced TNF-alpha production in human monocytic cells. Cells were stimulated by Stx1 or Stx2 (5 ng/ml) with or without CV6209 addition (12-100 microg/ml) for various periods of time. CV6209 significantly suppressed Stx-induced TNF-alpha production in a dose- and time-dependent manner. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that CV6209 suppressed Stx-mediated TNF-alpha mRNA expression. Our results indicated that CV6209 had an important regulatory effect on Stx-induced TNF-alpha production and gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Lymphocyte Activation / drug effects
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Pyridinium Compounds / pharmacology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Shiga Toxin 1 / toxicity
  • Shiga Toxin 2 / toxicity
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Pyridinium Compounds
  • RNA, Messenger
  • Shiga Toxin 1
  • Shiga Toxin 2
  • Tumor Necrosis Factor-alpha
  • CV 6209
  • L-Lactate Dehydrogenase