HIF-1 alpha inhibits T-2 toxin-mediated "immune evasion" process by negatively regulating PD-1/PD-L1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50019462" target="_blank" >RIV/62690094:18470/22:50019462 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0300483X22002360?pes=vor" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300483X22002360?pes=vor</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2022.153324" target="_blank" >10.1016/j.tox.2022.153324</a>

Jazyk výsledku

angličtina

Název v původním jazyce

HIF-1 alpha inhibits T-2 toxin-mediated "immune evasion" process by negatively regulating PD-1/PD-L1

Popis výsledku v původním jazyce

Trichothecene mycotoxins have a strong immunosuppressive effect, which may even escape host immune surveillance and damage the immune repair to show an “immune evasion&quot; effect. Increasing lines of evidence have shown that hypoxia and hypoxia-inducible factors (HIFs) are key mediators of trichothecenes, and these toxins appear to be closely related to the “immune evasion” mechanisms. Therefore, we used RAW264.7 cell model to explore the association of T-2 toxins with “immune evasion” process and hypoxia, as well as their cross-linking effects induced by T-2 toxin. Our results showed that HIF-1α is an important toxicity target of T-2 toxin, which could induce intracellular hypoxia. T-2 toxin induced an “immune evasion” process by activating the PD-1/PD-L1 signaling pathway. Interestingly, when HIF-1α activation was blocked, the “immune evasion” process regulated by PD-1/PD-L1 signaling was activated, resulting in the cells damage, suggesting that hypoxia induced by T-2 toxin plays a protective role for RAW264.7 cell damage. Thus, our work shows that HIF-1α inhibits T-2 toxin-mediated “immune evasion” process by negatively regulating PD-1/PD-L1signaling. This study contributes to a better understanding of the immunotoxicity mechanism of trichothecenes. © 2022 Elsevier B.V.

Název v anglickém jazyce

HIF-1 alpha inhibits T-2 toxin-mediated "immune evasion" process by negatively regulating PD-1/PD-L1

Popis výsledku anglicky

Trichothecene mycotoxins have a strong immunosuppressive effect, which may even escape host immune surveillance and damage the immune repair to show an “immune evasion&quot; effect. Increasing lines of evidence have shown that hypoxia and hypoxia-inducible factors (HIFs) are key mediators of trichothecenes, and these toxins appear to be closely related to the “immune evasion” mechanisms. Therefore, we used RAW264.7 cell model to explore the association of T-2 toxins with “immune evasion” process and hypoxia, as well as their cross-linking effects induced by T-2 toxin. Our results showed that HIF-1α is an important toxicity target of T-2 toxin, which could induce intracellular hypoxia. T-2 toxin induced an “immune evasion” process by activating the PD-1/PD-L1 signaling pathway. Interestingly, when HIF-1α activation was blocked, the “immune evasion” process regulated by PD-1/PD-L1 signaling was activated, resulting in the cells damage, suggesting that hypoxia induced by T-2 toxin plays a protective role for RAW264.7 cell damage. Thus, our work shows that HIF-1α inhibits T-2 toxin-mediated “immune evasion” process by negatively regulating PD-1/PD-L1signaling. This study contributes to a better understanding of the immunotoxicity mechanism of trichothecenes. © 2022 Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

1879-3185

Svazek periodika

480

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

11

Strana od-do

"Article number: 153324"

Kód UT WoS článku

000901662900003

EID výsledku v databázi Scopus

2-s2.0-85138619604