Deoxynivalenol upregulates hypoxia-inducible factor-1 & alpha; to promote an "immune evasion" process by activating STAT3 signaling
The result's identifiers
Result code in 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>
Alternative codes found
RIV/62690094:18470/23:50020567
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Deoxynivalenol upregulates hypoxia-inducible factor-1 & alpha; to promote an "immune evasion" process by activating STAT3 signaling
Original language description
Trichothecene mycotoxin deoxynivalenol (DON) negatively regulates immune response by damaging host immune system and harming the organism's health. We hypothesized that DON can initiate an active immunosuppressive mechanism similar to "immune evasion" 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 & alpha; (HIF-1 & alpha;) acts as a key regulator of DON-induced immunosuppression. HIF-1 & alpha; accumulated in the cytoplasm and was gradually transferred to the nucleus following DON treatment. Moreover, DON activated HIF-1 & 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 & 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 & 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Food and Chemical Toxicology
ISSN
0278-6915
e-ISSN
1873-6351
Volume of the periodical
179
Issue of the periodical within the volume
September
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
113975
UT code for WoS article
001051566500001
EID of the result in the Scopus database
2-s2.0-85166230347