• IMMUNE NETWORK
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• 제5권2호
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• pp.68-77
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• 2005

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

• IMMUNE NETWORK
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• 제19권1호
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• pp.1.1-1.13
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• 2019

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by production of autoantibodies to various nuclear antigens and overexpression of genes regulated by IFN-I called IFN signature. Genetic studies on SLE patients and mutational analyses of mouse models demonstrate crucial roles of nucleic acid (NA) sensors in development of SLE. Although NA sensors are involved in induction of antimicrobial immune responses by recognizing microbial NAs, recognition of self NAs by NA sensors induces production of autoantibodies to NAs in B cells and production of IFN-I in plasmacytoid dendritic cells. Among various NA sensors, the endosomal RNA sensor TLR7 plays an essential role in development of SLE at least in mouse models. CD72 is an inhibitory B cell co-receptor containing an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic region and a C-type lectin like-domain (CTLD) in the extracellular region. CD72 is known to regulate development of SLE because CD72 polymorphisms associate with SLE in both human and mice and CD72^-/- mice develop relatively severe lupus-like disease. CD72 specifically recognizes the RNA-containing endogenous TLR7 ligand Sm/RNP by its extracellular CTLD, and inhibits B cell responses to Sm/RNP by ITIM-mediated signal inhibition. These findings indicate that CD72 inhibits development of SLE by suppressing TLR7-dependent B cell response to self NAs. CD72 is thus involved in discrimination of self-NAs from microbial NAs by specifically suppressing autoimmune responses to self-NAs.

• IMMUNE NETWORK
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• 제12권5호
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• pp.176-180
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• 2012

Although the majority of research on CD137 has been directed to T cells, it is becoming clear that this molecule has distinct functions in other lineages of cells, including non-hematopoietic cells. In particular, emerging evidence suggests that the CD137-its ligand (CD137L) network involving immune cells and non-immune cells, directly or indirectly regulates inflammation in both positive and negative manners. Bidirectional signaling through both CD137 and CD137L is critical in the evolution of inflammation: 1) CD137L signaling plays an indispensible role in the activation and recruitment of neutrophils by inducing the production of proinflammatory cytokines and chemokines in hematopoietic and non-hematopoietic cells such as macrophages, endothelial cells and epithelial cells; 2) CD137 signaling in NK cells and T cells is required for their activation and can influence other cells participating in inflammation via either their production of proinflammatory cytokines or engagement of CD137L by their cell surface CD137: 3) CD137 signaling can suppress inflammation by controlling regulatory activities of dendritic cells and regulatory T cells. As recognition grows of the role of dysregulated CD137 or CD137L stimulation in inflammatory diseases, significant efforts will be needed to develop antagonists to CD137 or CD137L.

• Environmental Analysis Health and Toxicology
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• 제20권1호
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• pp.87-95
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• 2005

Cadmium is well known as a toxic metal and has insulin mimicking effects in rat adipose tissue. This study was undertaken to investigate the effect of CdCl₂ on glucose transport and its mechanism in 3T3 - L1 adipocytes. CdCl₂ exhibits respectively 2.2 and 2.8 fold increases in the 2-deoxyglucose uptake when exposed to 10 and 25 μM of CdCl₂ for 12 hr. To investigate the stimulating mechanism of glucose transport induced by CdCl₂. Wortmannin and PD98059 were used respectively as PI3K inhibitor and MAPK inhibitor, which did not affect 2-DOG uptake. This results suggest that induced 2-deoxy-(l-3H)-D-glucose (2-DOG) uptake by CdCl₂ may not be concerned with the insulin signalling pathway. Whereas nifedipine, a calcium channel blocker inhibited the 2- DOG uptake stimulated by CdCl₂. In addition, we also measured the increased production of Reactive oxygen substances (ROS) and glutathione (GSH) level in 3T3-L1 adipocytes to investigate correlation between the glucose uptake and increased production of ROS with H2DCFDA. CdCl₂ increased production of ROS. Induced 2-DOG uptake and increased production of ROS by CdCl₂ were decreased by N-acetylcystein (NAC). And L-buthionine sulfoximine (BSO) a potent inhibitor of γ-GCS, decreased of 2-DOG uptake. Also NAC and BSO changed the cellular GSH level, but GSH/GSSG ratio remained unchanged at 10, 25 μM of CdCl₂.

• IMMUNE NETWORK
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• 제14권2호
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• Journal of Microbiology and Biotechnology
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• 제21권5호
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• pp.529-535
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• 2011

Single-chain variable fragment (scFv) is a fusion protein of the variable regions of the heavy (VH) and light (VL) chains of immunoglobulin, connected with a short linker peptide of 10 to about 20 amino acids. In this study, the scFv of a monoclonal antibody against the third domain of human CD4 was cloned from OKT4 hybridoma cells using the phage display technique and produced in E. coli. The expression, production, and purification of anti-CD4 scFv were tested using SDS-PAGE and Western blot, and the specificity of anti-CD4 scFv was examined using ELISA. A 31 kDa recombinant anti-CD4 scFv was expressed and produced in bacteria, which was confirmed by SDS-PAGE and Western blot assays. Sequence analysis proved the ScFv structure of the construct. It was able to bind to CD4 in quality ELISA assay. The canonical structure of anti-CD4 scFv antibody was obtained using the SWISS_MODEL bioinformatics tool for comparing with the scFv general structure. To the best of our knowledge, this is the first report for generating scFv against human CD4 antigen. Engineered anti-CD4 scFv could be used in immunological studies, including fluorochrome conjugation, bispecific antibody production, bifunctional protein synthesis, and other genetic engineering manipulations. Since the binding site of our product is domain 3 (D3) of the CD4 molecule and different from the CD4 immunological main domain, including D1 and D2, further studies are needed to evaluate the anti-CD4 scFv potential for diagnostic and therapeutic applications.

• Journal of Animal Science and Technology
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• 제59권1호
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• pp.1.1-1.11
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• 2017

Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.

• 한국미생물·생명공학회지
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• 제19권5호
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• pp.514-520
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• 1991

Extrusion시켜 구조변형시킨 전분(질)을 기질로 cyclodextrin glucanotransferse(CGTase)를 활용하여 액화과정을 거치지 않고 직접 cyclodextrin을 합성하는 불용성 extrusion된 전분-수용성 CGTase로 구성된 불균일상 효소반응계에 관하여 연구하였다. Extrusion된 전분을 기질로 이용할 경우 기존의 액화전분을 기질로하는 균일상 효소반응계에서 보다 현저히 증가된 CD 농도, 수율 그리고 합성속도를 얻을 수 있었으며, extrusion된 전분 기질농도가 100g/l일 때 CD생성량과 수율은 각각 54g/l와 0.54였다.

• 멤브레인
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• 제8권3호
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• pp.170-176
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• 1998

가용성 전분으로부터 CGTase 효소에 의한 Cyclodextrin(CD) 동족체의 생산 실험을 dead-end형 막모듈을 설치한 막-효소 반응기에서 수행하였다. 회분 반응기에서의 CD 동족체 생산시 생산물 저해작용 및 생산된 CD의 다른 환원당으로의 분해에 의해 반응시간에 따른 전분의 CD 동족체로의 총 전환율이 최대 45%를 나타내었다가 급격히 감소하였다. 반면 분획분자량 10,000 달톤의 분리막이 설치된 막-효소 반응기에서의 CD 동족체 생산시 CD 동족체를 생산 즉시 반응기로부터 막을 통해 연속 분리할 수 있어 총 전환율이 35%로 일정하게 유지되었다. 10% 전분용액 및 2 atm 조작압력하에서 막-효소 반응기를 24시간 운전하였을 때 CD 동족체의 누적 생산량은 약 3.7 kg/m$^2$이었다.

• 한국수소및신에너지학회논문집
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• 제4권2호
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• pp.5-15
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• 1993

Hydrogen production in visible light with the following semiconductor systems, $CdS-WO_3$, $CdS-TiO_2$, have been investigated in the presence of redox catalyst (Pt, $RuO_2$). MeOH, EtOH, isopropanol, sulfide/sulfite mixture, lactic acid were used as sacrifical reagents. The optimal condition for $H_2$ evolution was found to be in qgueous lactic acid media for $CdS-WO_3/RuO_2$. The photochemical efficiency for this system was 1.05 % and the $H_2$ evolution rate was 26.5ml/min. at $6.07{\times}10^{-5}$ einstein/sec photon rate