• IMMUNE NETWORK
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• 제16권5호
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• pp.286-295
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• 2016

Cellular replicative senescence is a major contributing factor to aging and to the development and progression of aging-associated diseases. In this study, we sought to determine viral replication efficiency of influenza virus (IFV) and Varicella Zoster Virus (VZV) infection in senescent cells. Primary human bronchial epithelial cells (HBE) or human dermal fibroblasts (HDF) were allowed to undergo numbers of passages to induce replicative senescence. Induction of replicative senescence in cells was validated by positive senescence-associated b-galactosidase staining. Increased susceptibility to both IFV and VZV infection was observed in senescent HBE and HDF cells, respectively, resulting in higher numbers of plaque formation, along with the upregulation of major viral antigen expression than that in the non-senescent cells. Interestingly, mRNA fold induction level of virus-induced type I interferon (IFN) was attenuated by senescence, whereas IFN-mediated antiviral effect remained robust and potent in virus-infected senescent cells. Additionally, we show that a longevity-promoting gene, sirtuin 1 (SIRT1), has antiviral role against influenza virus infection. In conclusion, our data indicate that enhanced viral replication by cellular senescence could be due to senescence-mediated reduction of virus-induced type I IFN expression.

• 약학회지
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• 제41권3호
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• pp.365-369
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• 1997

Human chorionic gonadotropin (hCG) is a placental hormone and is involved in maintenance of the corpus luteum during pregnancy. In the present study, effect of hCG on nitiric ox ide (NO) generation from peritoneal macrophage was examined. hCG ahd no effect on NO generation by itself, whereas recombinant interferon- ${\gamma}$ (rIFN-${\gamma}$) alone had modest activity. When hCG was used in combination with rIFN-${\gamma}$, there was a marked cooperative induction of NO generation in a dose-dependent manner. The optimal effect of hCG on NO generation was shown at 6 hr after treatment with rIFN-${\gamma}$. Furthermore, northern blot analysis of showed that hCG increased the expression of inducible NO synthase(iNOS) gene. These results suggest that hCG induces NO generation from macrophages by increasing the expression of iNOS gene.

• 한국동물위생학회지
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• 제25권4호
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• pp.371-376
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• 2002

To determine the effect of picolinic acid on NOㆍ production, murine macrophages were incubated with either medium, various concentrations of picolinic acid, or IFN-${\gamma}$ plus picolinic acid for 48 hr. Picolinic acid does not induce NOㆍ production by itself, it acted synergistically with INF-${\gamma}$ for the induction of reactive nitrogen intermediate production in murine macrophages. Thymidine incorporation appeared to be reciprocally related to nitrite levels, suggesting that IFN-${\gamma}$ plus picolinic acid induced NOㆍ synthesis exerted antiproliferative effects.

• 미생물학회지
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• 제27권2호
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• pp.147-154
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• 1989

Vibrio vulnificus Lipopolysaccharide (LPS) was extracted, performed chemical analysis, tested its biological activities, and compared to those of Escherichia coli LPS and Salmonella typhimurium LPS. The lethal activity of V. vulnificus LPS was 138.6138.6 mg/kg in mouse, but this was lower than thowe of E. coli LPS (56.3 mg/kg) and S. typhimurium LPS (37.5 mg/kg). The result of fatty acid analysis showed that V. vulnificus LPS had more saturated fatty acid than E. coli LPS and S. typhimurium LPS. Above results indicated that V. vulnificus LPS did not have much effect on the lethality. The results of biological responses of enzymes and blood cells by LPSs showed that V. vulnificus LPS had slightly greater activity than E. coli LPS and S. typhimurium LPS. V. vulnificus LPS was recommendavle for stimulant on interferon induction because of adequate stimulation and safety for host and cell lines.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1554-1562
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• 2018

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

• IMMUNE NETWORK
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• 제8권1호
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• pp.7-12
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• 2008

Background: Members belonging to the interferon-lambda (IFN-${\lambda}$) family exert protective action against viral infection; however, the mechanisms of their action have remained elusive. To study IFN-${\lambda}$ biology, such as endocytosis of IFN-${\lambda}$, we produced monoclonal antibodies (Abs) against human IFN-${\lambda}$ and examined their usefulness. Methods: We purified recombinant human IFN-${\lambda}$1 expressed in Escherichia coli by using affinity columns. Then, we generated hybridoma cells by fusing myeloma cells with splenocytes from IFN-${\lambda}$1-immunized mice. For evaluating the neutralizing activity of the monoclonal Abs against IFN-${\lambda}$1, we performed RT-PCR for the MxA transcript. In order to study the binding activity of IFN-${\lambda}$ and the monoclonal Ab complex on HepG2 cells, we labeled the monoclonal Ab with rhodamine and determined the fluorescence intensity. Results: Four hybridoma clones secreting Abs specific to IFN-${\lambda}$1 were generated and designated as HL1, HL2, HL3, and HL4. All the Abs reacted with IFN-${\lambda}$1 in the denatured form as well as in the native form. Abs produced by HL1, HL3, and HL4 did not neutralize the induction of the MxA gene by IFN-${\lambda}$1. We also demonstrated the binding of the HL1 monoclonal anbitody and IFN-${\lambda}$ complex on HepG2 cells. Conclusion: Monoclonal Abs against IFN-${\lambda}$1 were produced. These Abs can be used to study the cellular binding and internalization of IFN-${\lambda}$.

• Journal of Acupuncture Research
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• 제23권4호
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• pp.205-218
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• 2006

Objectives : This study was performed to investigate the effects of anti-cancer and changes In immune response of Lonicerge Flos Herbal-acupuncture. Methods Experimental studies were evaluated through the anti-cancer and immune response activities such as, cell viability, BNA fragmentation, Apoptosis, survival time, pulmonary colonization, and productivity of interleukins & $interferon-{\gamma}$. In order to study the effects of anti-cancer and changes in immune response of Lonicerae Flos Herbal-acupuncture, the groups were divided into five groups ; Normal group(non treated group), Control A group(0.2ml Normal saline for oral administration), Control B group(administration of intramuscular injection with 0.2ml Lonicerae Flos Herbal-acupuncture solution), Acupuncture group(AT, administration of acupuncture at Chungbu(L1)), and Herbal-Acupuncture group(HAT, administration of Lonicerae Flos Herbal-acupuncture at Chungbu(L1)). Results : 1. Lonicerae Flos Herbal-acupuncture(>300mg/ml) could lead cancer cell to cell death. 2. Lonicerae Flos Herbal - acupuncture (40mg/ml) caused DNA cleavage. 3. Lonicerae Flos Herbal-acupuncture(400mg/ml) caused apoptosis in the cancer cell line. 4. In mouse survival time, all of experimental groups didn't show any significant compared to the control group. 5. In pulmonary colonization assay, Lonicerae Flos Herbal-acupuncture group was less than Control A group at 7 days after induction of cancer. 6. In comparison Control A group, there was significant decrease of Interleukin-2 level in Lonicerae Flos Herbal-acupuncture group. 7. In comparison Control group, there was decrease of Interleukin-4 level in the Acupuncture group. 8. In comparison Control group, there was decrease of Interleukin-10 level in the Acupuncture group. 9. In comparison Control group, there was significant increase of Interleukin-12 level in Acupuncture group and Lonicerae Flos Herbal-acupuncture group. 10. In comparison Control group, there was significant increase of $Interferon-{\gamma}$ level in Acupuncture group. Conclusion : According to above mentioned results, Lonicerae Flos Herbal- acupuncture is expected to be effective for anticancer and improvement in immune response.

• Journal of Microbiology and Biotechnology
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• 제29권12호
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• pp.2014-2021
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• 2019

Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the genus Betacoronavirus and causes severe morbidity and mortality in humans especially when infected patients have underlying diseases such as chronic obstructive pulmonary disease (COPD). Previously, we demonstrated that MERS-CoV-encoded ORF8b strongly inhibits MDA5- and RIG-I-mediated induction of the interferon beta (IFN-β) promoter activities. Here, we report that ORF8b seemed to regulate MDA5 or RIG-I differentially as protein levels of MDA5 were significantly down-regulated while those of RIG-I were largely unperturbed. In addition, ORF8b seemed to efficiently suppress phosphorylation of IRF3 at the residues of 386 and 396 in cells transfected with RIG-I while total endogenous levels of IRF3 remained largely unchanged. Furthermore, ORF8b was able to inhibit all forms of RIG-I; full-length, RIG-I-1-734, and RIG-I-1-228, the last of which contains only the CARD domains. Taken together, it is tempting to postulate that ORF8b may interfere with the CARD-CARD interactions between RIG-I and MAVS. Further detailed analysis is required to delineate the mechanisms of how ORF8b inhibits the MDA5/RIG-I receptor signaling pathway.

• 미생물학회지
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• 제38권4호
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• pp.203-203
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• 2002

Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

• Molecules and Cells
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• 제38권5호
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• pp.441-451
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• 2015

Recognition of cytosolic DNA initiates a series of innate immune responses by inducing IFN-I production and subsequent triggering JAK1-STAT1 signaling which plays critical roles in the pathogenesis of infection, inflammation and autoimmune diseases through promoting B cell activation and antibody responses. The stimulator of interferon genes protein (STING) has been demonstrated to be a critical hub of type I IFN induction in cytosolic DNA-sensing pathways. However, it still remains unknown whether cytosolic DNA can directly activate the JAK1-STAT1 signaling or not. And the role of STING is also unclear in this response. In the present study, we found that dsDNA directly triggered the JAK1-STAT1 signaling by inducing phosphorylation of the Lyn kinase. Moreover, this response is not dependent on type I IFN receptors. Interestingly, STING could inhibit dsDNA-triggered activation of JAK1-STAT1 signaling by inducing SHP-1 and SHP-2 phosphorylation. In addition, compared with normal B cells, the expression of STING was significantly lower and the phosphorylation level of JAK1 was significantly higher in B cells from MRL/lpr lupus-prone mice, highlighting the close association between STING low-expression and JAK1-STAT1 signaling activation in B cells in autoimmune diseases. Our data provide a molecular insight into the novel role of STING in dsDNA-mediated inflammatory disorders.