• Journal of Pharmaceutical Investigation
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• v.17 no.4
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• pp.213-216
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• 1987

The distribution features of recombinant human $alpha-interferon(rHuIFN-{\alpha}A)$ and $^{14}C-radiolabeled\;rHuIFN-{\alpha}A\;(^{14}C-rHuIFN-{\alpha}A)$ were investigated in ICR mice after i.v. injection. The level of $rHuIFN-{\alpha}A$ in the kidney was significantly higher than those in lung and liver at 10min after the injection. But the level was reduced significantly at 60min. The level of radioactivity in the kidney was also significantly higher than those in other organs after i.v. injection of $^{14}C-rHuIFN-{\alpha}A$, but it was reduced at much slower speed than was $rHuIFN-{\alpha}A$. These results show that interferon is distributed repidly and the kidney is the main site of distribution and metabolism of $rHuIFN-{\alpha}A$.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.813-818
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• 2002

Expression of monokine induced by IFN-$\gamma$(Mig) mRNA is well-known to strictly depend on Interferon-$\gamma$(IFN-$\gamma$). Lipopolysaccharide (LPS) alone Is weakly effective on Mig mRNA expression in mouse Peritoneal macrophages. This study was undertaken to investigate the synergistic effect of LPS and IFN-$\beta$ on chemokine Mig gene expression in mouse peritoneal macrophages. Although IFN-$\beta$ alone was minimally effective, LPS plus IFN-$\beta$ synergized to produce a high level of Mig mRNh. The synergistic effect of LPS and IFN-$\beta$ (LPS/IFN-$\beta$) on Mig mRNA expression was strain-specific. The most effective synergistic effect of LPS/IFN-$\beta$ on the mRNh expression was found in simultaneous stimulation of LPS/IFN-$\beta$. This synergy was modulated at the level of the gene transcription and was not dependent on a new protein synthesis. Synergistic effect of LPS/IFN-$\beta$ also required the activation of $NF-_KB$. Accordingly, these data suggest that LPS/IFN-$\beta$ synergizes the expression of Mig mRNA through a process that depends on a pretranscriptional level and/or coincident Mig mRNA transcription.

• Journal of Animal Science and Technology
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• v.51 no.6
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• pp.471-484
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• 2009

The peri-implantation period in mammals is critical with respect to survival of the conceptus (embryo/fetus and associated extraembryonic membranes) and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. At this time, interferon tau (IFNT) is synthesized and secreted by the mononuclear trophectodermal cells of the conceptus between days 10 and 21~25. The actions of IFNT to signal pregnancy recognition and induce or increase expression of IFNT-stimulated genes (ISGs), such as ISG15 and OAS, are mediated by the Type I IFN signal transduction pathway. This article reviews the history, signaling pathways of IFNT and the uterine expression of several IFNT-stimulated genes during the peri-implantation period. Collectively, these newly identified genes are believed to be critical to unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for successful implantation and pregnancy.

• Journal of Microbiology
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• v.41 no.4
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• pp.295-299
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• 2003

Adenovirus (Ad) precursor to the terminal protein (pTP) plays an essential roles in the viral DNA replication. Ad pTP serves as a primer for the synthesis of a new DNA strand during the initiation step of replication. In addition, Ad pTP forms organized spherical replication foci on the nuclear matrix (NM) and anchors the viral genome to the NM. Here we identified the interferon inducible gene product 1-8D (Inid) as a pTP binding protein by using a two-hybrid screen of a HeLa cDNA library. Of the clones obtained in this assay, nine were identical to the Inid, a 13-kDa polypeptide that shares homology with genes 1-8U and Leu-13/9-27, most of which have little known functions. The entire open reading frame (ORF) of Inid was cloned into the tetracycline inducible expression vector in order to determine the biological functions related with adenoviral infection. When Inid was introduced to the cells along with adenoviruses, fifty to sixty percent of Ad-infected cells expressing Inid had rounded morphology, which was suggestive of apoptosis. Results from the terminal deoxynucleotidyl transferase (TdT) and DNA fragmentation assays confirmed that Inid induces apoptosis in Ad-infected or in uninfected cells. The Inid binding to pTP may target the cell for apoptotic destruction as a host defense mechanism against the viral infection.

• Toxicological Research
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• v.12 no.1
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• pp.87-91
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• 1996

LB00013, a newly developed recombinant human Interferon $\beta$, was tested for primary eye and skin irritation in male New Zealand White rabbits. In the primary eye irritation test, 0.1 ml of a solution of LB00013 was instilled into the eye. In the rinsing group, the eye was washed with water at 30 seconds after instillation. No reaction was produced at the cornea, iris and conjunctivae by LB00013. In the primary skin irritation test, LB00013 was applied to the back of rabbits for 24 hours. Primary irritation index was "0" in test and control sites of all animals. Thus LB00013 was evaluated as a non-irritant on the basis of the criteria of Draize et al. (1944).l. (1944).

• Toxicological Research
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• v.12 no.1
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• pp.81-86
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• 1996

Antigenicity of recombinant human interferon $\beta$(LB00013), a newly developed drug for anti-cancer and anti-viral therapeutic use, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LB00013 sensitized with aluminum hydroxide gel (Alum) as an adjuvant, when judged by the heterologous passive cutaneous anaphylaxis (PCA) test in rats. Meanwhile, antibodies against ovalbumin (OVA) sensitized with Alum were clearly detected. 2. In guinea pigs, the sensitization of neither LB00013 only nor LB00013 with complete Freund's adjuvant (CFA) produced positive reactions in the homologous active systemic anaphylaxis (ASA) and the PCA tests. Meanwhile, the sensitization of OVA with CFA produced positive reactions in both PCA and ASA. 3. A LB00013-specific reaction was not observed in an indirect hemagglutination(IHA) assay using sera isolated from LB00013 sensitized mice. The present results suggested that LB00013 may have no antigenic potential in mice and guinea pigs.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.130-136
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• 1999

Mouse guanylate-binding protein 3 (mGBP3) is a 71-kDa GTPase which belongs to GTP-binding protein family. The present study showed that the expression of mGBP3 transcript was readily induced in a dose dependent fashion in the macrophage cell line RAW264.7 treated with either $interferon-{\gamma} (IFN-\gamma)$ or lipopolysaccaride (LPS). The expression of mGBP3 protein was also apparent by 4 and 6 h after the treatment of cells with IFN-\gamma (100 U/ml) or LPS ($1{\mu}g/ml$) , and remained at palteau for at least 24 h. Cycloheximide ($10{\mu}g/ml$) had no effect on the $IFN-\gamma-$ or LPS-induced mGBP3 expression, suggesting that the mGBP3 induction did not require further protein synthesis. Interestingly, a protein kinase C (PKC) inhibitor staurosporine (50 nM) abolished the induction of mGBP3 expression by LPS, but not by $IFN-{\gamma}$. These findings suggest that mGBP3 may be involved in the macrophage activation process and both IFN-\gamma and LS induce the mGBP3 expression through distinct signal transduction pathways.

• Clinical and Experimental Pediatrics
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• v.62 no.3
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• pp.108-112
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• 2019

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha ($IFN-{\alpha}$) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of $IFN-{\alpha}$ therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular $IFN-{\alpha}$ therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular $IFN-{\alpha}$ treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular $IFN-{\alpha}$ treatment in patients with SSPE.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1137-1143
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• 2019

Hepatitis E virus (HEV) accounts for 20 million infections in humans worldwide. In most cases, the infections are self-limiting while HEV genotype 1 infection cases may lead to lethal infections in pregnant women (~ 20% fatality). The lack of small animal models has hampered detailed analysis of virus-host interactions and HEV-induced pathology. Here, by employing a recently developed culture-adapted HEV, we demonstrated that methyltransferase, a non-structural protein, strongly inhibits melanoma differentiation-associated gene 5 (MDA5)-mediated activation of type I interferon responses. Compared to uninfected controls, HEV-infected cells display significantly lower levels of $IFN-{\beta}$ promoter activation when assessed by luciferase assay and RT-PCR. HEV genome-wide screening showed that HEV-encoded methyltransferase (MeT) strongly inhibits MDA5-mediated transcriptional activation of $IFN-{\beta}$ and $NF-{\kappa}B$ in a dose-responsive manner whether or not it is expressed in the presence/absence of a tag fused to it. Taken together, current studies clearly demonstrated that HEV MeT is a novel antagonist of MDA5-mediated induction of $IFN-{\beta}$ signaling.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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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.