• The Journal of Engineering Geology
• /
• v.3 no.1
• /
• pp.39-49
• /
• 1993

Intrinsic random function of order k(IRF-k) was used to estimate groundwater levels of nonstationaav random functions. The accuracy of IRF-k was compared to that of ordraarv krigrng assuming that the data of groundwater levels compose a stafionarv random function. Cross validation and statistical errors show that IRF-k is superior to orcinarv '(riging for the estimation of water levels. IRF-k and ordinary kriging made different contour and 3-D surface maps. The maps of IRF-k are more accurate than those of ordinary kriging.

• Biomolecules & Therapeutics
• /
• v.31 no.1
• /
• pp.48-58
• /
• 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.

• BMB Reports
• /
• v.54 no.9
• /
• pp.482-487
• /
• 2021

Interferon regulatory factors (IRFs) play roles in various biological processes including cytokine signaling, cell growth regulation and hematopoietic development. Although it has been reported that several IRFs are involved in bone metabolism, the role of IRF2 in bone cells has not been elucidated. Here, we investigated the involvement of IRF2 in RANKL-induced osteoclast differentiation. IRF2 overexpression in osteoclast precursor cells enhanced osteoclast differentiation by regulating the expression of NFATc1, a master regulator of osteoclastogenesis. Conversely, IRF2 knockdown inhibited osteoclast differentiation and decreased the NFATc1 expression. Moreover, IRF2 increased the translocation of NF-κB subunit p65 to the nucleus in response to RANKL and subsequently induced the expression of NFATc1. IRF2 plays an important role in RANKL-induced osteoclast differentiation by regulating NF-κB/NFATc1 signaling pathway. Taken together, we demonstrated the molecular mechanism of IRF2 in osteoclast differentiation, and provide a molecular basis for potential therapeutic targets for the treatment of bone diseases characterized by excessive bone resorption.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.50 no.3
• /
• pp.302-310
• /
• 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.

• BMB Reports
• /
• v.47 no.10
• /
• pp.558-562
• /
• 2014

OASL1 is a member of the 2'-5'-oligoadenylate synthetase (OAS) family and promotes viral clearance by activating RNase L. OASL1 interacts with the 5'-untranslated region (UTR) of interferon regulatory factor 7 (Irf7) and inhibits its translation. To identify the secondary structure required for OASL1 binding, we examined the 5'-UTR of the Irf7 transcript using "selective 2'-hydroxyl acylation analyzed by primer extension" (SHAPE). SHAPE takes advantage of the selective acylation of residues in single-stranded regions by 1-methyl-7-nitroisatoic anhydride (1M7). We found five major acylation sites located in, or next to, predicted single-stranded regions of the Irf7 5'-UTR. These results demonstrate the involvement of the stem structure of the Irf7 5'-UTR in the regulation of Irf7 translation, mediated by OASL1.

• Korean Journal of Veterinary Research
• /
• v.44 no.2
• /
• pp.195-200
• /
• 2004

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic side effects. Interferon (IFN)-${\gamma}$ often modulates the anti-cancer activities of TNF family members including TRAIL. We previously reported that IFN-${\gamma}$ enhanced TRAIL-induced Apoptosis in HeLa cells without the unknown mechanism. In this study, we investigated whether IRF-1 involves in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis. We exposed HeLa cells to IFN-${\gamma}$ for 12 hours and then treated with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with IFN-${\gamma}$, and TRAIL only induced 30% apoptosis after 3 hours treatment. In HeLa cells pretreated with IFN-${\gamma}$, TRAIL induced cell death to more than 75% at 3 hours, showed that IFN-${\gamma}$-pretreatment enhanced HeLa cell death to TRAIL-induced apoptosis. To investigate the functional role of IRF-1 in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis, IRF-1 was overexpressed by using an adenoviral vector AdIRF-1. IRF-1 overexpression increased apoptotic cell death and significantly enhanced apoptotic cell death induced by TRAIL when infected cells were treated with TRAIL. Our findings show that IFN-${\gamma}$ enhances TRAIL-induced apoptosis by IRF-1 in HeLa cells.

• Journal of fish pathology
• /
• v.36 no.2
• /
• pp.213-228
• /
• 2023

We evaluated the transcriptional response of interferon (IFN)-related genes in rock bream iridovirus (RBIV)-infected rock bream under high-, low-, or no-mortality conditions induced by different stocking water temperatures. Under the high susceptibility condition (group A, water temperature 26℃, 100% mortality), only the Mx gene was expressed early, with prolonged expression, and with heavy viral loads of approximately 10⁶~10⁷ major capsid protein gene copies/μL from 4 to 10 days post infection (dpi). However, IRF1, IRF3, IRF8, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56 were activated at later time points (8 dpi) and then quickly decreased (10 dpi). For the low susceptibility condition, the water temperature was set at 23℃ for 7 days (group B) and then reduced to 17℃. Group B exhibited a 28% mortality rate, in which persistent and effective antiviral responses were observed for long periods of time. In particular, at 20 and 22 dpi, when virus replication was peaked at approximately 10⁷/μL, the expressions of most of the IFN-related genes (IRF1, IRF3, IRF8, Mx, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56) were significantly higher in group B than in the control group. Moreover, prolonged and higher levels of IRF3 (at least 30 dpi), IRF8 (at least 30 dpi), ISG15 (at least 30 dpi), PKR (at least 28 dpi), Viperin (at least 30 dpi), and IFI44 (at least 30 dpi) were also observed in the recovery stage of infection. Under the no-susceptibility condition at 17℃ (0% mortality), significantly elevated levels of IRF3, Mx, ISG15, and PKR were observed mostly until 20 dpi. The findings indicate that RBIV infection can induce an efficient IFN-mediated antiviral immune response in low- and no-susceptibility conditions. The findings could be valuable for effective control of viral pathogens in fish.

• Journal of fish pathology
• /
• v.34 no.1
• /
• pp.23-29
• /
• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.5
• /
• pp.547-554
• /
• 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.

• Journal of the Korean Society for Aeronautical & Space Sciences
• /
• v.44 no.2
• /
• pp.131-138
• /
• 2016

In this paper, we studied the IRF performances of the chirp signal used in the SAR system. The most important factors that degrade IRF performances are amplitude and phase errors. Each factor can be represented to linear, quadratic, random and ripple terms. That can be extracted by a quadratic polynomial curve fitting of chirp waveform. We analyzed the IRF performances by the error terms and supposed the minimum value of RF non-linearity to meet the specification of the PSLR and ISLR.