• 한국어병학회지
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• 제34권1호
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• pp.23-29
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• 2021

Interferon regulatory factors (IRFs) are a family of transcription factors essential to the control of antiviral immune response, cell growth, differentiation and apoptosis. IRF10 of zebrafish (Danio rerio) was negative regulation of the interferonΦ1 and 3 response in vitro. In this study, we analyze the induction of in vivo immune response activation from the IRF10 gene of zebrafish and the protective effect against VHSV. As the results, the group inoculated with IRF10 expression vectors, there was no expression of IFNΦ1, suggestion that IRF10 may function as a negative regulator of IRF3, which binds to the IFNΦ1 promoter. And other types of interferon genes (IFNΦ2-4) are thought to have been activated, inducing to the expression of pro-inflammatory cytokine and Mx genes. As the results of challenge test performed at 14 days after inoculation of the expression vectors, the maximum survival rate [50% (1㎍ DNA) and 42.5% (10㎍ DNA)] for IRF10 group were recorded. Meanwhile, the survival rates of pcDNA3.1 and PBS as the control groups were 10% and 15%, respectively. This study suggests that the possibility that activation of IRF10 molecule could be exploited as a VHS control method.

• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.235-244
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• 2021

Interferon Regulatory Factor 3 (IRF3) is a member of interferon-regulated transcription factor family and is known to play an important role in the innate immune response against viral infections. In this study, the expression of IRF3 in different tissues, developmental stages, and stocking densities of olive flounder was investigated. The expression of IRF3 was observed to gradually increase in early-stage juvenile fish. The highest expression was observed in later-stage juvenile fish when immune tissues were formed. High IRF3 expression was observed in the muscles and the brain tissues. The expression of IRF3 was observed in fish at different stocking densities after viral hemorrhagic septicemia virus (VHSV) infection. It yielded an interesting expression pattern in the muscles and the brain tissues of fish stocked at low density. These observations can be used as basic data for the study of the expression of immune response-related genes against viruses based on stocking density and immune systems in other fish species.

• 한국수산과학회지
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• 제50권3호
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• pp.302-310
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• 2017

Interferon regulatory factor 8 (IRF8) is essential for the development of B and T cells, as well as for the activity of dendritic cells and macrophages. We performed molecular characterization of IRF8 from rock fish, Sebastes schlegelii (Ss), and investigated the spatial and temporal profile of mRNA expression after challenge with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C), or Streptococcus iniae. The full-length cDNA sequence of SsIRF8 was 1,657 bp, containing an ORF of 1,266 bp. The gene had a predicted molecular mass of 47.7 kDa and an isoelectric point of 5.99. The amino acid sequence coded by this gene showed the highest degree of identity (90.8%) and similarity (96.2%) with IRF8 from Oplegnathus fasciatus. The SsIRF8 mRNA was expressed ubiquitously, at varying levels, with the highest level of expression observed in the spleen. To confirm the role of SsIRF8 in mediating the immune response, we measured SsIRF8 mRNA expression in the splenic tissue at different time points after injection with LPS, poly I:C, or S. iniae. The qRT-PCR results showed that SsIRF8 mRNA expression in the poly I:C-injected group was highly upregulated 6 hr after exposure (P<0.05). Expression of SsIRF8 mRNA in the S. iniae-injected group peaked at 24 hr. These results suggest that SsIRF8 might be important in regulating the strength of the rockfish immune response to immunostimulatory agents.

• 대한한의학방제학회지
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• 제16권2호
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• pp.219-228
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• 2008

Objective : The present study was designed to investigate whether the water extract of the root of Scutellaria baicalensis could regulate lipopolysaccharide (LPS)-induced type 1 interferon. Methods : To evaluate of type 1 interferon inhibitory effect of the root of Scutellaria baicalensis, we examined type 1 interferon in LPS-stimulated RAW264.7 cells. Furthermore, Interleukin (IL)-10 and interferon regulatory factor (IRF) - 1, 7 expression level were examined to study the inhibition mechanisms. Results 1. Extract from the root of Scutellaria baicalensis didn't have any cytotoxity itelf. 2. Extract from the root of Scutellaria baicalensis inhibited interferon-a,b in dose dependant- and type 1 interferon production in time dependant manner. 3. Extract from the root of Scutellaria baicalensis reduced IL-10 and IRF-1, 7 production in LPS-stimulated RAW 264.7 cells. Conclusion : The extract from the root of Scutellaria baicalensis down-regulated LPS-induced type 1 interferon through suppression of IL-10 and IRF-1, 7 expression. This results suggested that the extract from the root of Scutellaria baicalensis may be a beneficial drug against inflammatory diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제21권5호
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• pp.547-554
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• 2017

Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon $(IFN)-{\beta}$ mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF) and TANK-binding kinase 1 (TBK1). A mechanism study revealed that HQ inhibited IRF-3 phosphorylation induced by lipopolysaccharide (LPS), TRIF, and AKT by suppressing phosphorylation of AKT, an upstream kinase of the IRF-3 signaling pathway. IRF-3 phosphorylation is highly induced by wild-type AKT and poorly induced by an AKT mutant, AKT C310A, which is mutated at an inhibitory target site of HQ. We also showed that HQ inhibited IRF-3 phosphorylation by targeting all three AKT isoforms (AKT1, AKT2, and AKT3) in RAW264.7 cells and suppressed IRF-3-mediated luciferase activities induced by AKT in HEK293 cells. Taken together, these results strongly suggest that HQ inhibits the production of a type I IFN, $IFN-{\beta}$, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.48-58
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• 2023

Interferon regulatory factor 3 (IRF3) integrates both immunological and non-immunological inputs to control cell survival and death. Small GTPases are versatile functional switches that lie on the very upstream in signal transduction pathways, of which duration of activation is very transient. The large number of homologous proteins and the requirement for site-directed mutagenesis have hindered attempts to investigate the link between small GTPases and IRF3. Here, we constructed a constitutively active mutant expression library for small GTPase expression using Gibson assembly cloning. Small-scale screening identified multiple GTPases capable of promoting IRF3 phosphorylation. Intriguingly, 27 of 152 GTPases, including ARF1, RHEB, RHEBL1, and RAN, were found to increase IRF3 phosphorylation. Unbiased screening enabled us to investigate the sequence-activity relationship between the GTPases and IRF3. We found that the regulation of IRF3 by small GTPases was dependent on TBK1. Our work reveals the significant contribution of GTPases in IRF3 signaling and the potential role of IRF3 in GTPase function, providing a novel therapeutic approach against diseases with GTPase overexpression or active mutations, such as cancer.

• 대한한방부인과학회지
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• 제26권2호
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• pp.17-32
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• 2013

Objectives: The purpose of this study was to investigate whether Lonicera japonica(LJ) could inhibit LPS-induced type I IFN production. Methods: To evaluate inhibitory effect of LJ on type I IFN, we examined type I IFN, IRF-1, 7 and IL-10 production on LPS-induced macrophages using real time RT-PCR. Next, we observed the interaction of type I IFN, IRF-1, 7 and IL-10 using IL-10 neutralizing antibody. Finally we examined the activation of STAT-1, 3 using western blot. Results: LJ inhibited Type I IFN expression of mRNA and increased IL-10 expression of mRNA. Also LJ inhibited the level of IRF-1, 7 mRNA and the nuclear translocation of IRF-3. Further more, LJ reduced the activation of STAT-1, 3 which are involved in continuous secretion of immune cytokines. Blockade of IL-10 action caused a significant reduction of type I IFN and IRF-1, 7 than LPS-induced LJ pretreatment. Conclusions: LJ inhibits LPS-induced production of type I IFN by IL-10. This study may provide a clinical basis for anti-inflammatory properties of LJ.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.226-232
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• 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• 동의생리병리학회지
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• 제23권5호
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• pp.986-992
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• 2009

Type I interferons (IFNs) are critical mediators of the innate immune system to defend viral infection. Interferon regulatory factor (IRF) and signal transducer and activator of transcription (STAT) play critical roles in type I IFN production in response to viral infection. Luteolin is natural polyphenolic compounds that have anti-inflammatory, cytoprotective and anti-carcinogenic effects. However, the mechanism of action and impact of luteolin on innate immunity is still unknown. In this study, we examined the effects of luteolin on the lipopolysacchride (LPS)-induced inflammatory responses. Luteolin inhibited Type I IFNs expression of mRNA and increased interleukin(IL)-10 expression of mRNA. Next, we examined the protective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action didn't cause a significant reduction of Type I IFNs than LPS-induced luteolin pretreatment. Pretreatment of luteolin inhibited the level of IRF-1, and IRF-7 mRNA and the nuclear translocation of IRF-3. Also, luteolin reduced the activation of STAT - 1, 3. Theses results suggest that luteolin inhibits LPS-induced the production of Type I IFNS by both IRFs and STATs not IL-10 and may be a beneficial drug for the treatment of inflammatory disease.