Pseurotin D Inhibits the Activation of Human Lymphocytes

J 2021

Pseurotin D Inhibits the Activation of Human Lymphocytes

RUBANOVÁ, Daniela, Petra DAĎOVÁ, Ondřej VAŠÍČEK a Lukáš KUBALA

Základní údaje

Originální název

Pseurotin D Inhibits the Activation of Human Lymphocytes

Autoři

RUBANOVÁ, Daniela (203 Česká republika, domácí), Petra DAĎOVÁ (203 Česká republika, domácí), Ondřej VAŠÍČEK (203 Česká republika, domácí) a Lukáš KUBALA (203 Česká republika, garant, domácí)

Vydání

International Journal of Molecular Sciences, Basel, MDPI, 2021, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.208

Kód RIV

RIV/00216224:14310/21:00121494

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.3390/ijms22041938

UT WoS

000623785200001

Klíčová slova anglicky

pseurotin; lymphocyte; STAT3; STAT5; proliferation

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 8. 2021 16:23, Mgr. Marie Šípková, DiS.

Anotace

V originále

Background: Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological activities including the modulation of immune response. Purpose: Complex characterization of the effects of pseurotin D on human lymphocyte activation in order to understand the potential of pseurotin to modulate immune response in humans. Methods: CD4+ and CD8+ T cells and CD19+ B cells isolated from human blood were activated by various activators simultaneously with pseurotin D treatment. The effects of pseurotin were tested on the basis of changes in cell viability, apoptosis, activation of signal transducers and activators of transcription (STAT) signaling pathways, production of tumor necrosis factor (TNF)-alpha by T cells, expression of activation markers CD69 and CD25 on T cells and Human Leukocyte Antigen-DR isotype (HLA-DR) on B cells, and the differentiation markers CD20, CD27, CD38, and immunoglobulin (Ig) D on B cells. Results: Pseurotin D significantly inhibited the activation of both CD4+ and CD8+ human T cells complemented by the inhibition of TNF-alpha production without significant acute toxic effects. The Pseurotin D-mediated inhibition of T-cell activation was accompanied by the induction of the apoptosis of T cells. This corresponded with the inhibited phosphorylation of STAT3 and STAT5. In human B cells, pseurotin D did not significantly inhibit their activation; however, it affected their differentiation. Conclusions: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of lymphocytes and suggest pseurotins as new attractive chemotypes for future research in the context of immune-modulatory drugs.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

MUNI/C/0013/2019, interní kód MU

Název: Charakterizace vlivu pseurotinů na specifickou imunitní odpověď

Investor: Masarykova univerzita, Charakterizace vlivu pseurotinů na specifickou imunitní odpověď, DO R. 2020 - Program rektora

Citovat

RUBANOVÁ, Daniela, Petra DAĎOVÁ, Ondřej VAŠÍČEK a Lukáš KUBALA. Pseurotin D Inhibits the Activation of Human Lymphocytes. International Journal of Molecular Sciences. Basel: MDPI, 2021, roč. 22, č. 4, s. 1-14. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms22041938.

@article{1764159,
   author = {Rubanová, Daniela and Daďová, Petra and Vašíček, Ondřej and Kubala, Lukáš},
   article_location = {Basel},
   article_number = {4},
   doi = {http://dx.doi.org/10.3390/ijms22041938},
   keywords = {pseurotin; lymphocyte; STAT3; STAT5; proliferation},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Pseurotin D Inhibits the Activation of Human Lymphocytes},
   url = {https://www.mdpi.com/1422-0067/22/4/1938},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1764159
AU  - Rubanová, Daniela - Daďová, Petra - Vašíček, Ondřej - Kubala, Lukáš
PY  - 2021
TI  - Pseurotin D Inhibits the Activation of Human Lymphocytes
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 4
SP  - 1-14
EP  - 1-14
PB  - MDPI
SN  - 14220067
KW  - pseurotin
KW  - lymphocyte
KW  - STAT3
KW  - STAT5
KW  - proliferation
UR  - https://www.mdpi.com/1422-0067/22/4/1938
N2  - Background: Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological activities including the modulation of immune response. Purpose: Complex characterization of the effects of pseurotin D on human lymphocyte activation in order to understand the potential of pseurotin to modulate immune response in humans. Methods: CD4+ and CD8+ T cells and CD19+ B cells isolated from human blood were activated by various activators simultaneously with pseurotin D treatment. The effects of pseurotin were tested on the basis of changes in cell viability, apoptosis, activation of signal transducers and activators of transcription (STAT) signaling pathways, production of tumor necrosis factor (TNF)-alpha by T cells, expression of activation markers CD69 and CD25 on T cells and Human Leukocyte Antigen-DR isotype (HLA-DR) on B cells, and the differentiation markers CD20, CD27, CD38, and immunoglobulin (Ig) D on B cells. Results: Pseurotin D significantly inhibited the activation of both CD4+ and CD8+ human T cells complemented by the inhibition of TNF-alpha production without significant acute toxic effects. The Pseurotin D-mediated inhibition of T-cell activation was accompanied by the induction of the apoptosis of T cells. This corresponded with the inhibited phosphorylation of STAT3 and STAT5. In human B cells, pseurotin D did not significantly inhibit their activation; however, it affected their differentiation. Conclusions: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of lymphocytes and suggest pseurotins as new attractive chemotypes for future research in the context of immune-modulatory drugs.
ER  -

RUBANOVÁ, Daniela, Petra DAĎOVÁ, Ondřej VAŠÍČEK a Lukáš KUBALA. Pseurotin D Inhibits the Activation of Human Lymphocytes. \textit{International Journal of Molecular Sciences}. Basel: MDPI, 2021, roč.~22, č.~4, s.~1-14. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms22041938.

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