Identification of NF-AT-like transcription factor in Schistosoma mansoni: its possible involvement in the antiparasitic action of cyclosporin A.
Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of protozoan and helminth parasites. In schistosomes, evidence has been accumulated to propose that the drug damages parasites by mechanisms independent of its immunosuppressive properties. Moreover, the absence of correlation between anti-schistosomal properties and inhibition of peptidyl-prolyl cis-trans isomerase activity of cyclophilins (CsA receptors) for various drug analogs, argued against a direct implication of cyclophilins in the lethal effect of CsA. We describe, in S. mansoni, the existence of NF-AT-like transcription factors, a protein family already characterized by its sensitivity to CsA. The observation that CsA treatment of S. mansoni larvae inhibited the expression of the Sm28GST protein and the characterization of a functional NF-AT-like site in the gene encoding this protein, provide new insights in the understanding of the antischistosomal effect of CsA. Our results also support the hypothesis that the regulatory function of NF-AT-like proteins might be responsible for parasite development and survival in the host and open new perspectives in studies of helminth biology.
Unite 167 INSERM, Institut Pasteur, Lille, France.
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D000818:Animals; D001483:Base Sequence; D016572:Cyclosporine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011817:Rabbits; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D012556:Schistosomicides / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012556:Schistosomicides; D014157:Transcription Factors; D016572:Cyclosporine; D005982:Glutathione Transferase