• Molecules and Cells
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• v.24 no.2
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• pp.247-254
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• 2007

Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.

• Advances in Traditional Medicine
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• v.4 no.3
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• pp.163-170
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• 2004

The effect of immune activation by Echinacea purpurea was investigated by measuring total immunoglobulin (Ig) G, IgM. and the radioprotective effect of immune activation by Echinacea purpurea was investigated by measuring T lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Echinacea purpurea activated macrophages to stimulate $IFN-{\gamma}$ production in association with the secondary activation of T lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Echinacea purpurea administration activated helper T cells to proliferate. In addition, activated macrophages in association with the secondary T lymphocyte activation increased $IFN-{\gamma}$ production and stimulated proliferation of cytotoxic T cells and suppressor T cells, indicating the activation of cell-mediated immune responses.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.87-87
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• 2020

In this study, we investigated the immune-enhancing activity of water extracts from Hydrangea macrophylla subsp. serrata (WE-HML). WE-HML increased cell viability and production of immunomodulators, which contributed to activating phagocytic activity in RAW264.7 cells. Inhibition of JNK and NF-κB reduced the production of immunomodulators by WE-HML. ROS inhibition suppressed the production of immunomodulators, and the activation of JNK and NF-κB signaling by WE-HML. TLR4 inhibition attenuated the production of immunomodulators, and activation of JNK and NF-κB signaling by WE-HML. In the immunosuppressed mouse model, WE-HML increased the spleen index, the levels of the cytokines, the numbers of white blood cells, lymphocytes, and neutrophils. However, WE-HML inhibited LPS-mediated overproduction of pro-inflammatory mediators in RAW264.7 cells, which indicated that WE-HML may have anti-inflammatory activity under excessive inflammatory conditions. Taken together, WE-HML may be considered to have immune-enhancing activity and expected to be used as a potential immune-enhancing agent.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.201-205
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• 2002

It is generally accepted that the immune system is one of the major target organs for many toxic chemicals. In addition, many toxic chemicals require metabolic activation by cytochrome P450s for their toxicity. Although the immune cells possess a limited amount of drug metabolizing capacity, metabolic activation of certain toxicants in liver and immune organs may have a significant role in immunosuppression. In the present studies, the possible role of metabolic activation by cytochrome P450s in chemical-induced immunosuppression was reviewed, with a particular emphasis on the methodological techniques to detect immunotoxicants requiring metabolic activation in vivo and in vitro. (omitted)

• Toxicological Research
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• v.33 no.4
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• pp.283-290
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• 2017

The host immune system is the first line of host defense, consisting mainly of innate and adaptive immunity. Immunity must be maintained, orchestrated, and harmonized, since overactivation of immune responses can lead to inflammation and autoimmune diseases, while immune deficiency can lead to infectious diseases. We investigated the regulation of innate and adaptive immune cell activation by Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin, and scopolin). Macrophage phagocytic activity was determined using fluorescently labeled Escherichia coli, as an indicator of innate immune activation. Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte proliferation was analyzed as surrogate markers for cellular and humoral adaptive immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS-induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside did not show such activity. These results indicate that A. capillaris and its components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS-induced adaptive immune cell activation. The results suggest that A. capillaris is useful as a regulator of adaptive immunity for diseases involving excessive immune response activation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.88-88
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• 2020

Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng. In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG. WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1β, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition. Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.115-121
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• 2009

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of posttranscriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation.

• BMB Reports
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• v.55 no.10
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• pp.473-480
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• 2022

Neutrophils, the most abundant innate immune cells, play essential roles in the innate immune system. As key innate immune cells, neutrophils detect intrusion of pathogens and initiate immune cascades with their functions; swarming (arresting), cytokine production, degranulation, phagocytosis, and projection of neutrophil extracellular trap. Because of their short lifespan and consumption during immune response, neutrophils need to be generated consistently, and generation of newborn neutrophils (granulopoiesis) should fulfill the environmental/systemic demands for training in cases of infection. Accumulating evidence suggests that neutrophils also play important roles in the regulation of adaptive immunity. Neutrophil-mediated immune responses end with apoptosis of the cells, and proper phagocytosis of the apoptotic body (efferocytosis) is crucial for initial and post resolution by producing tolerogenic innate/adaptive immune cells. However, inflammatory cues can impair these cascades, resulting in systemic immune activation; necrotic/pyroptotic neutrophil bodies can aggravate the excessive inflammation, increasing inflammatory macrophage and dendritic cell activation and subsequent T_H1/T_H17 responses contributing to the regulation of the pathogenesis of autoimmune disease. In this review, we briefly introduce recent studies of neutrophil function as players of immune response.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.230-239
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• 2012

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.

• Childhood Kidney Diseases
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• v.12 no.1
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• pp.23-29
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• 2008

Kidney allograft transplantation is the most effective method of renal replacement for end stage renal disease patients. Still, it is another kind of 'disease', requiring immunosuppression to keep the allograft from rejection(allograft immune reaction). Immune system of the allograft recipient recognizes the graft as a 'pathogen (foreign or danger)', and the allograft-recognizing commanderin-chief of adaptive immune system, T cell, recruits all the components of immune system for attacking the graft. Proper activation and proliferation of T cell require signals from recognizing proper epitope(processed antigen by antigen presenting cell) via T cell receptor, costimulatory stimuli, and cytokines(IL-2). Thus, most of the immunosuppressive agents suppress the process of T cell activation and proliferation.