Inhibition of Shiga toxin-induced tumor necrosis factor-alpha production and gene expression in human monocytic cells
H M Zhang1, M Ohmura, F Gondaira
1Department of Bacteriology, Niigata University School of Medicine, Japan. zhanghm@med.niigata-u.ac.jp
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.
Insights
CV6209, a PAF antagonist, effectively reduced tumor necrosis factor-alpha (TNF-alpha) production and gene expression in human cells exposed to Shiga toxin (Stx). This suggests CV6209 may help manage STEC infections.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) is crucial in Shiga toxin-producing Escherichia coli (STEC) pathogenesis.
- Shiga toxins (Stx) induce inflammatory responses, contributing to STEC infection severity.
Purpose of the Study:
- To investigate the effect of CV6209, a platelet-activating factor (PAF) antagonist, on Stx-induced TNF-alpha production.
- To determine if CV6209 can modulate TNF-alpha gene expression in human monocytic cells stimulated with Stx.
Main Methods:
- Human monocytic cells were stimulated with Stx1 or Stx2 in the presence or absence of CV6209.
- TNF-alpha production was measured over various time points.
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze TNF-alpha mRNA expression.
Main Results:
- CV6209 significantly suppressed Stx-induced TNF-alpha production in a dose- and time-dependent manner.
- CV6209 treatment led to a reduction in Stx-mediated TNF-alpha mRNA expression.
- The PAF antagonist CV6209 demonstrated a regulatory effect on Stx-induced inflammatory responses.
Conclusions:
- CV6209 exhibits potent inhibitory effects on Stx-induced TNF-alpha production and gene expression.
- These findings suggest CV6209 as a potential therapeutic agent for managing STEC infections by modulating key inflammatory pathways.