Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00072951" target="_blank" >RIV/00159816:_____/20:00072951 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216224:14110/20:00115426
Výsledek na webu
<a href="https://jlb.onlinelibrary.wiley.com/doi/full/10.1002/JLB.4VMA0318-138R" target="_blank" >https://jlb.onlinelibrary.wiley.com/doi/full/10.1002/JLB.4VMA0318-138R</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/JLB.4VMA0318-138R" target="_blank" >10.1002/JLB.4VMA0318-138R</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes
Popis výsledku v původním jazyce
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-alpha, 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.
Název v anglickém jazyce
Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes
Popis výsledku anglicky
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-alpha, 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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10601 - Cell biology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of leukocyte biology
ISSN
0741-5400
e-ISSN
—
Svazek periodika
107
Číslo periodika v rámci svazku
3
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
12
Strana od-do
497-508
Kód UT WoS článku
000515440500012
EID výsledku v databázi Scopus
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