Deoxynivalenol upregulates hypoxia-inducible factor-1 & alpha; to promote an "immune evasion" process by activating STAT3 signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10469245" target="_blank" >RIV/00179906:_____/23:10469245 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/23:50020567

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rJCu.taaBh" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rJCu.taaBh</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.fct.2023.113975" target="_blank" >10.1016/j.fct.2023.113975</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Deoxynivalenol upregulates hypoxia-inducible factor-1 & alpha; to promote an "immune evasion" process by activating STAT3 signaling

Popis výsledku v původním jazyce

Trichothecene mycotoxin deoxynivalenol (DON) negatively regulates immune response by damaging host immune system and harming the organism&apos;s health. We hypothesized that DON can initiate an active immunosuppressive mechanism similar to &quot;immune evasion&quot; to alter the cellular microenvironment and evade immune surveillance. We tested this hypothesis using the RAW264.7 macrophage model. DON rapidly increased the expression of immune checkpoints PD-1 and PD-L1, inflammatory cytokine TGF-8, and key immune evasion factors STAT3, VEGF, and TLR-4, and caused cellular hypoxia. Importantly, hypoxia-inducible factor-1 &amp; alpha; (HIF-1 &amp; alpha;) acts as a key regulator of DON-induced immunosuppression. HIF-1 &amp; alpha; accumulated in the cytoplasm and was gradually transferred to the nucleus following DON treatment. Moreover, DON activated HIF-1 &amp; alpha; through STAT3 signaling to upregulate downstream signaling, including PD-1/PD-L1. Under DON treatment, immunosuppressive miR-210-3p, lncRNA PVT1, lncRNA H19, and lncRNA HOTAIR were upregulated by the STAT3/HIF-1 &amp; alpha; axis. Moreover, DON damaged mitochondrial function, causing mitophagy, and suppressed immune defenses. Collectively, DON triggered RAW264.7 intracellular hypoxia and rapidly activated HIF-1 &amp; alpha; via STAT3 signaling, activating immune evasion signals, miRNAs, and lncRNAs, thereby initiating the key link of immune evasion. This study offers further clues for accurate prevention and treatment of immune diseases caused by mycotoxins.

Název v anglickém jazyce

Deoxynivalenol upregulates hypoxia-inducible factor-1 & alpha; to promote an "immune evasion" process by activating STAT3 signaling

Popis výsledku anglicky

Trichothecene mycotoxin deoxynivalenol (DON) negatively regulates immune response by damaging host immune system and harming the organism&apos;s health. We hypothesized that DON can initiate an active immunosuppressive mechanism similar to &quot;immune evasion&quot; to alter the cellular microenvironment and evade immune surveillance. We tested this hypothesis using the RAW264.7 macrophage model. DON rapidly increased the expression of immune checkpoints PD-1 and PD-L1, inflammatory cytokine TGF-8, and key immune evasion factors STAT3, VEGF, and TLR-4, and caused cellular hypoxia. Importantly, hypoxia-inducible factor-1 &amp; alpha; (HIF-1 &amp; alpha;) acts as a key regulator of DON-induced immunosuppression. HIF-1 &amp; alpha; accumulated in the cytoplasm and was gradually transferred to the nucleus following DON treatment. Moreover, DON activated HIF-1 &amp; alpha; through STAT3 signaling to upregulate downstream signaling, including PD-1/PD-L1. Under DON treatment, immunosuppressive miR-210-3p, lncRNA PVT1, lncRNA H19, and lncRNA HOTAIR were upregulated by the STAT3/HIF-1 &amp; alpha; axis. Moreover, DON damaged mitochondrial function, causing mitophagy, and suppressed immune defenses. Collectively, DON triggered RAW264.7 intracellular hypoxia and rapidly activated HIF-1 &amp; alpha; via STAT3 signaling, activating immune evasion signals, miRNAs, and lncRNAs, thereby initiating the key link of immune evasion. This study offers further clues for accurate prevention and treatment of immune diseases caused by mycotoxins.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Food and Chemical Toxicology

ISSN

0278-6915

e-ISSN

1873-6351

Svazek periodika

179

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

113975

Kód UT WoS článku

001051566500001

EID výsledku v databázi Scopus

2-s2.0-85166230347