Inhibition of Shiga toxin-induced tumor necrosis factor-alpha production and gene expression in human monocytic cells by CV6209.
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.
Zhang
H M
HM
Department of Bacteriology, Niigata University School of Medicine, Japan. zhanghm@med.niigata-u.ac.jp
Ohmura
M
M
Gondaira
F
F
Yamamoto
T
T
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022622:Shiga Toxin 1 / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000633:toxicity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D011726:Pyridinium Compounds; D012333:RNA, Messenger; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014409:Tumor Necrosis Factor-alpha; C053321:CV 6209; D007770:L-Lactate Dehydrogenase