• Archives of Pharmacal Research
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• v.15 no.1
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• pp.20-29
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• 1992

Effects of squalene on cellular and non-specific immune responses and antitumor activity in mice were investigated. Cellular and non-specific immunological assay parameters adopted in the present study were delayed-type hypersensitivity reaction and resette forming cells (RFC) for cellular immunity, activities of natural killer (NK) cells and phagocyte for non-specific immunity. Squalene resulted in marked increases of cellular and non-specific immune functions and enhancement of host resistance to tumor challenge in dose-dependent manner.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.229-236
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• 2004

Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma, small cell lung carcinoma and neuroblastoma. Immunity against GD2 has anti-tumor activities, but GD2 is poorly immunogenic. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In our previous study, we produced anti-idiotypic antibodies mimicking GD2 (3A4 and 3H9), which induced humoral immunity. However, cellular immunity is essential to eradicate tumor cells in vivo as well as humoral immunity. In the present study, we investigated whether these anti-idiotypic antibodies 3A4 and 3H9 could induce cellular immunes responses. Methods: BALB/C mice were immunized with anti-idiotypic antibody 3A4 or 3H9, or normal mouse IgG as a negative control. Lymphoproliferative responses, cytokine production responses, and delayed-type hypersensitivity reactions were measured in mice immunized with the anti-idiotypic antibodies. Results: Both the anti-idiotypic antibody 3A4 and 3H9 induced GD2-specific lymphoproliferative responses and $IFN-{\gamma}$ production of lymph node lymphocytes in BALB/C mice. Only anti-idiotypic antibody 3H9 induced significant GD2-specific delayed-type hypersensitivity in the mice. Conclusion: These results show that anti-idiotypic antibodies 3A4 and 3H9 have the potentiality of inducing GD2-specific cellular immune responses that cannot be induced by the native antigen GD2 itself.

• Molecules and Cells
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• v.21 no.1
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• pp.121-128
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• 2006

Maitotoxin (MTX) is known as one of the most potent marine toxins involved in Ciguatera poisoning, but intracellular signaling pathways caused by MTX was not fully understood. Thus, we have investigated whether intracellular reactive oxygen species (ROS) are involved in MTX-induced cellular responses in human umbilical vein endothelial cells. MTX induced a dose-dependent increase of intracellular [$Ca^{2+}$]. MTX stimulated the production of intracellular ROS in a dose- and time-dependent manner, which was suppressed by BAPTA-AM, an intracellular $Ca^{2+}$ chelator. Ionomycin also elevated the ROS production in a dose-dependent manner. MTX elevated transamidation activity in a time-dependent manner and the activation was largely inhibited by transfection of tissue transglutaminase siRNA. The activation of tissue transglutaminase and ERK1/2 by MTX was suppressed by BAPTA-AM or ROS scavengers. In addition, MTX-induced cell death was significantly delayed by BAPTA-AM or a ROS scavenger. These results suggest that [$Ca^{2+}$]-dependent generation of intracellular ROS, at least in part, play an important role in MTX-stimulated cellular responses, such as activation of tTGase, ERK phosphorylation, and induction of cell death, in human umbilical vein endothelial cells.

• YAKHAK HOEJI
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• v.36 no.2
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• pp.93-109
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• 1992

The purpose of this experiment was to investigate both the immunomodulatory effect of evening primrose(EP) oil and the effects of EP oil on immunoregulation by cyclophosphamide in mice. EP oil at doses of 0.1, 0.2 and 0.4 ml/kg were orally administered to ICR male mice once daily for 28 consecutive days. Cyclophosphamide was injected intraperitoneally to ICR mice with a single dose of 5 mg/kg at 2 days before secondary immunization. Mice were sensitized and challenged with sheep red blood cells(S-RBC). Immnune responses were evaluated by humoral and cellular immune responses and non-specific immune response. The results of this study were summarized as follows; (1) The humoral immune responses such as hemagglutination titer(HA), hemolysin titer(HY), Arthus reaction and plaque forming cell(PFC) were significantly enhanced in the low dose EP oil administered groups(0.1 and 0.2 ml/kg). However, in the high dose EP oil administered group(0.4 ml/kg) the responses were significantly lowered. (2) In the case of cellular immune responses, delayed type hypersensitivity reaction(DTH) was significantly decreased in EP oil whereas rosette forming cell(RFC) was remarkably enhanced. (3) Activities of natural killer cells and phagocyte were generally enhanced in EP oil. In addition, serum albumin and globulin were also increased.

• BMB Reports
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• v.52 no.2
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• pp.127-132
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• 2019

Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses.

• BMB Reports
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• v.42 no.9
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• pp.574-579
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• 2009

The regulatory effects of honokiol on the cellular responses of macrophages and monocytes were evaluated. Specifically, we investigated the effects of honokiol with respect to lipopolysaccharide (LPS)-induced cytotoxicity, LPS- or phorbol-12-myristate-13-acetate (PMA)-mediated morphological changes, and relevant events (FITC-dextran-induced phagocytic uptake). Honokiol blocked the LPS-induced cytotoxicity of RAW264.7 cells in a dose-dependent manner. In addition, honokiol appeared to block the production of cytotoxic cytokines such as interleukin (IL)-$1{\beta}$ and tumor necrosis factor (TNF)-$\alpha$, nitric oxide (NO), and reactive oxygen species (ROS). Moreover, honokiol strongly prevented the morphological changes in RAW 264.7 and U937 cells that were induced by LPS and PMA. The surface levels of marker proteins, which are up-regulated under the morphological changes of RAW264.7 and U937 cells, were also diminished. The data presented here strongly suggest that the honokiol modulates various cellular responses managed by macrophages and monocytes.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.267-270
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• 1995

We examined the chronic effect of dextromethorphan(DM) on the cellular immune responses in mice. T cell simulator, phytohemagglutinin did not show singificant effect on lymphocyte proliferation. Costimulator of T and B cell, pokeweed mitogen, and B cell stimulator, lipopolysaccharide exhibited DM-induced decreased lymphocyte proliferation. Singificantly suppressed natural killer (NR) cell cytotoxicity was evidenced following 6 months DM exposure. These results suggest that chronic DM administration pertub B cell functioning and NK cell cytotoxicity. In addition, prenatal DM exposure did not potentiate the immunomodulation in postnatal effect induced by chronic DM.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• YAKHAK HOEJI
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• v.46 no.1
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• pp.52-57
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• 2002

Effects of the butanl fraction of Astragali Radix (BFAR) on the cellular and nonspecific immune responses were investigated in ICR mice. Mice were divided into 4 groups and BFAR at doses of 5, 25 and 125 mg/kg u ere administered orally to mice daily for 3 weeks, and the normal animals were given vehicle. The results of this study are summarized as follows; the relative weight of thymus was greatly increased by BFAR treatment, compared with that in mormal mice. However, the body weight gain was not affected. Delayed-type hypersensitivity (DTH) reaction to sheep red blood cells (SRBC) for cellular immunity was significantly enhanced by BFAR treatment, compared with those in normal mice. In these mice, BFAR also dose-dependently increased activities of phagocyte and natural killer (NK) cells as well as the number of leukocyte resulted from nonspecific immunity Thus, these results demonstrate that BFAF treatment results in a significant increase in both cellular and nonspecific immune responses to antigen in concentrations that enhance humoral immune function.

• Molecules and Cells
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• v.27 no.1
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• pp.5-14
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• 2009

The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of long-term T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.