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Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes
K. Bendíčková, F. Tidu, M. De Zuani, MH. Kohoutková, I. Andrejčinová, A. Pompeiano, S. Bělášková, G. Forte, T. Zelante, J. Frič,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- antifungální látky metabolismus MeSH
- Aspergillus fumigatus účinky léků MeSH
- C-reaktivní protein metabolismus MeSH
- chemokiny metabolismus MeSH
- cyklosporin farmakologie MeSH
- inhibitory kalcineurinu farmakologie MeSH
- interleukin-10 metabolismus MeSH
- lidé MeSH
- monocyty účinky léků metabolismus MeSH
- myeloidní buňky účinky léků metabolismus MeSH
- myši MeSH
- sekvence nukleotidů MeSH
- sekvenční homologie aminokyselin MeSH
- sérový amyloidový protein metabolismus MeSH
- signální transdukce účinky léků MeSH
- THP-1 buňky MeSH
- TNF-alfa metabolismus MeSH
- transkripční faktory NFATC metabolismus MeSH
- transport proteinů účinky léků MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Calcineurin (CN) inhibitors are effective clinical immunosuppressants but leave patients vulnerable to potentially fatal fungal infections. This study tested the hypothesis that CN inhibition interferes with antifungal immune defenses mediated by monocytes. We showed that NFAT is expressed by human monocytes, and is activated by exposure to fungal ligands. We confirmed that NFAT translocation potently activated target gene transcription using a human monocytic reporter cell line. Inhibition of CN-NFAT by cyclosporine A significantly reduced monocyte production of TNF-α, IL-10, and MCP-1 proteins in response to pattern recognition receptor ligands as well as to Aspergillus fumigatus conidia. Moreover, we revealed that human monocytes express the antifungal protein pentraxin-3 under control of NFAT. In conclusion, clinical CN inhibitors have the potential to interfere with the novel NFAT-dependent pentraxin-3 pathway as well as antifungal cytokine production in human monocytes, thereby impeding monocyte-mediated defenses against fungal infection in immune-suppressed patients.
Department of Experimental Medicine University of Perugia Perugia Italy
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
Citace poskytuje Crossref.org
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