Irf3 from mandarin fish thymus initiates interferon transcription

Chen, Xiaowu; Shen, Yawei; Wu, Minxian; Zhao, Jianmin

doi:10.1007/s10695-018-0543-8

Cited by 8 publications

(3 citation statements)

References 56 publications

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“…qPCR was conducted using SYBR Green Premix Ex Taq (Takara) in a CFX96 real-time PCR system (Bio-Rad, Hercules, CA, USA) as in our previous work [55]. β-actin was used as an internal reference.…”

Section: Methodsmentioning

confidence: 99%

Expression and Functional Analysis of Hepcidin from Mandarin Fish (Siniperca chuatsi)

Shen

Zhao

Zhao³

et al. 2019

IJMS

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Hepcidin is a liver-derived peptide hormone that is related to iron balance and immunity in humans. However, its function in Siniperca chuatsi has not been well elucidated. In this study, we analyzed the expression and function of the S. chuatsi hepcidin (Sc-hep) gene. Sc-hep was specifically expressed in the liver and appeared to be one of the most highly expressed genes in the liver. After spleen and kidney necrosis virus (ISKNV) infection and lipopolysaccharide (LPS) and polyinosinic—polycytidylic acid (Poly I:C) stimulation, the expression of Sc-hep in the liver increased by approximately 110, 6500, and 225 times, respectively. After ferrous sulfate (FS) injection, the expression of Sc-hep in the liver increased approximately 520-fold. We found that miR-19c-5p could inhibit Sc-hep expression. Five CpG dinucleotides distributed in the promoter region showed no differential methylation between the liver and the stomach, both presenting high methylation rates. After FS or LPS injection, the expression of three iron balance-related genes (FPN1, TFR1, and FTN) and five immune-related cytokine genes (IL-1β, IL8, TNF-α, TLR22, and SOCS3) significantly changed. These results indicate that Sc-hep participates in the regulation of iron balance and plays an important role in the immune system. Sc-hep increased approximately 52-fold when mandarin fish were domesticated with artificial diets. Sc-hep might be used as a real-time biomarker of mandarin fish liver because its expression markedly varies under different physiological conditions.

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Section: Methodsmentioning

confidence: 99%

Expression and Functional Analysis of Hepcidin from Mandarin Fish (Siniperca chuatsi)

Shen

Zhao

Zhao³

et al. 2019

IJMS

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“…Ключевые транскрипционные пептидные факторы, участвующие в регуляции иммунного ответа, такие как NF-κB (nuclear factor kappalight-chain-enhancer of activated B cells), JAK-STAT (Janus kinase -signal transducer and activator of transcription) и IRFs (interferon regulatory factors), были изначально обнаружены у костистых рыб. Критическими регуляторами IFN типа I являются IRF3 и IRF7, а IRF1, IRF5 и IRF8 запускают IFN-ответы клеточно-специфическим образом [16]. В работе R. Pandey и соавт.…”

Section: Introductionunclassified

Influence of alpha-glutamil-tryptophan on the background and induced activity of factors of adaptive immunity for prevention

Ruleva,

Krasnov,

Petlenko

et al. 2024

Acta biomedica scientifica

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Background. During the ongoing COVID-19 pandemic and in the season of rising incidence of other respiratory infections, it is relevant to use preventive measures of non-specific prophylaxis. Synthetic peptides are widely considered as a tool. The representative of this group is the synthetic analogue of thymus regulatory peptides Thymogen, which has been used in Russia for more than 20 years in the treatment of acute and chronic infection diseases.The aim of the study. To evaluate the effect of Thymogen, a dosed nasal spray, on induced parameters of the immune system during prophylactic use in healthy volunteers.Materials and methods. Twenty healthy volunteers received Thymogen nasal dosed spray (JSC “Cytomed”, Russia) at a dose of 25 μg twice a day for 10 days. A comparative assessment of immunological parameters was carried out in dynamics: before the start of therapy, on days 6 and 11 of taking the drug and 14 days after the end of the course. Clinical observation was carried out from day 1 to day 11, registration of adverse events – the entire period of the study for 24 days. The first day was considered the day the drug was started.Results. In the course of the work, according to the data of immunological examination, a statistically significant increase in the virus-induced production of interferon alpha (INF-α) by a culture of peripheral blood cells was revealed. The growth rate was recorded on day 11 of taking Thymogen and persisted for 14 days after the end of the course. Significant differences in the dynamics of bactericidal and phagocytic activity of neutrophils, serum α- and γ-interferon were not obtained.Conclusion. The use of Thymogen spray at a dose of 25 μg for 10 days was safe and contributed to a significant induction of interferon-alpha in response to exposure to a viral pathogen, which allows us to recommend the drug for prophylactic use during the period of rising incidence of acute respiratory diseases.

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“…In addition, the structures of the phosphorylation sites are divergent in fish and mammals, resulting in different activation mechanisms (23). Overall, fish IRF3 functions as a crucial transcription factor for the activation of IFN expression to defend against viral influence with species specificity (24,25).…”

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confidence: 99%

Zebrafish Uba1 Degrades IRF3 through K48-Linked Ubiquitination to Inhibit IFN Production

Chen

Jiang

et al. 2021

The Journal of Immunology

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Fish IFN regulatory factor 3 (IRF3) is a crucial transcription factor in the IFN activation signaling pathway, which leads to IFN production and a positive cycle. Unrestricted IFN expression results in hyperimmune responses and therefore, IFN must be tightly regulated. In the current study, we found that zebrafish Ub-activating enzyme (Uba1) negatively regulated IRF3 via the K-48 ubiquitin proteasome degradation of IRF3. First, ifn expression stimulated by spring viraemia of carp virus infection was blunted by the overexpression of Uba1 and enhanced by Uba1 knockdown. Afterward, we found that Uba1 was localized in the cytoplasm, where it interacted with and degraded IRF3. Functional domains analysis revealed that the C-terminal ubiquitin-fold domain was necessary for IRF3 degradation by Uba1 and the N-terminal DNA-binding domain of IRF3 was indispensable for the degradation by Uba1.The degradation of IRF3 was subsequently impaired by treatment with MG132, a ubiquitin proteasome inhibitor. Further mechanism analysis revealed that Uba1 induced the K48-linked Ub-proteasomal degradation of IRF3. Finally, the antiviral capacity of IRF3 was significantly attenuated by Uba1. Taken together, our study reveals that zebrafish Uba1 interacts with and activates the ubiquitinated degradation of IRF3, providing evidence of the IFN immune balance mechanism in fish.

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Irf3 from mandarin fish thymus initiates interferon transcription

Cited by 8 publications

References 56 publications

Expression and Functional Analysis of Hepcidin from Mandarin Fish (Siniperca chuatsi)

Expression and Functional Analysis of Hepcidin from Mandarin Fish (Siniperca chuatsi)

Influence of alpha-glutamil-tryptophan on the background and induced activity of factors of adaptive immunity for prevention

Zebrafish Uba1 Degrades IRF3 through K48-Linked Ubiquitination to Inhibit IFN Production

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