• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.866-874
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• 2006

Atopic dermitiis(AD) is a chronic inflammatory skin disease, which requires safe and effective medicinal therapy. Over production of Th2 cytokines and chemokines as well as IgE, which are mediated by highly activated immune cells, have been considered as pathologic factors in this disease. We found that Gamipaidok-san(GPDS), which is a traditional herbal medicine clinically prescribing for atopic dermitis patients in the hospital, has suppressive effects on the development of DNC8 induced dermatitis in Nc/Nga atopic model. Oral administration of GPDS at the concentration of 250 mg/Kg for 12 weeks significantly suppressed the clinical severity of the dermatitis including pruities, edema, eczematous and dryness. Histological examination revealed that thickness of dermis and epidermis were considerably reduced, and the number of infiltrated inflammatory immune cells including mast cells, CCR3+, and CD4+ T cells were decreased in the affected skin and ear, and consistantly, the number of CD3+/CCR3+ cells in Iymph nodes were decreased. The levels of Th2 cytokines produced by activated splenocyte from atopic mice were also down-regulated by GPDS. Furthermore, the serum levels of IgE were considerably reduced, which accompanied by a decrease in the number of B220+IgE+ B cells in the Iymph nodes. Taken together, these results suggested that oral administration of GPDS, a traditional herbal medicine, has suppressive effects on atopic dermitis of Nc/Nga mouse by the modulation of the immune system, therefore GPDS has potential as a natural therapeutic for treatment of atopic dermatitis.

• Korean Journal of Pharmacognosy
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• v.21 no.4
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• pp.307-316
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• 1990

This study was undertaken to test the effects of Daturae Flos(DF) and Daturae Semen(DS) on the cellular and humoral immune responses, and the functions of the cells involved in immunoinflammation. Both extracts decreased the activity of superoxide dismutase, and the decrease was greater in the mouse group which was treated with DS. Both extracts decreased the phagocytic activity as measured by assessing the number of the latex particle within the phagocyte after incubation of peritoneal macrophages with fluorochrome-labelled latex particle and decreased natural killer cell activity as measured by enumerating the viable YAC-1 cells after treatment of target cells with splenic natural killer cells. Both extracts also decreased the cell-mediated immunity in vivo as assessed by measuring the ear thickness after sensitization and challenge with dinitrofluorobenzene, however, had no effects on the humoral immune responses as measured by checking hemolysin and hemagglutinin titers after immunization with sheep red blood cells(SRBC). Extracts of Semen caused decrease in the number of rosette forming cells between the splenic cells and SRBC. The results of this study suggested that both Daturae extracts could depress the immunoinflammation by affecting the various cell types involved in inflammation.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.23.1-23.16
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• 2021

Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.150-157
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• 2009

This research was performed in order to investigate the anti-inflammatory effects of Bupleuri Radix(BR) on the Immune response in vitro. Cellular proliferation and cytokine production were measured in mast cells or mouse B cells or CD4 Th cells. BR water extract inhibited the secretions of TNF-$\alpha$ and IL-6 in PMA/A23187 stimulated HMC-1 cells. It increased proliferation but did not affect the expressions of CD69 or CD23 in rIL-4/anti-CD40 activated S cells. BR reduced surface IgE expression and secreted IgE but increased the production of IL-4, IFN-$\gamma$ and IgG1 in the same cells. BR caused an increase in proliferation in anti-CD3/anti-CD28 stimulated CD4 Th cells but it did not affect the differentiation of Th1 or Th2 cells. However, IL-2 was increased in BR treated Th2 cells. Considering the above-mentioned results, BR can be applied to a broad range of anti-inflammatory reactions, but our data suggest that it will not be likely to exert any effects on type 1 allergic response.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.79-98
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• 1999

The purpose of this Study was to investigate effect of TakliSodokSan(TSS) on the anti-tumor, immunocytes and nitric oxide(NO) production from mice peritoneal macrophages. This Study estimated the proliferation of L1210 cell lines, A431 cell lines, Hep-G2 cell lines, K562 cell lines, 3T3 cell lines, mouse thymocytes and mouse splenocytes and NO production from pcritoneal macrophages in vitro, and estimated the proliferation of L1210 cells, thymocytes and splenocytcs, NO production from peritoneal macrophages and body weight in L1210 cells-transplanted mice in vivo. The results were obtained as follows; 1. TSS inhibited significantly the proliferation of L1210, A431, Hep-G2, K562 cell lines in vitro. 2. TSS accelerated the proliferation of mice thymocytes and splenocytes in vitro. 3. TSS was not increased the nitric oxide production from mice peritoneal macrophages in vitro. 4. TSS inhibited significantly the proliferation of L1210 cells in Ll210 cells∼transplanted mice. 5. TSS accelerated the proliferation of mice thymocytes and splenocytes In L1210 cells-transplanted mice. 6. TSS was increased significantly the nitric oxide production from mice peritoneal macrophages in L1210 cells-transplanted mice. 7. TSS was increased the body weight as comparing with control group in Ll210 cells-transplanted mice.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.279-287
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• 2018

Placenta specific 8 (PLAC8, also known as ONZIN) is a multi-functional protein that is highly expressed in the intestine, lung, spleen, and innate immune cells, and is involved in various diseases, including cancers, obesity, and innate immune deficiency. Here, we generated a Plac8 knockout mouse using the CRISPR/Cas9 system. The Cas9 mRNA and two single guide RNAs targeting a region near the translation start codon at Plac8 exon 2 were microinjected into mouse zygotes. This successfully eliminated the conventional translation start site, as confirmed by Sanger sequencing and PCR genotyping analysis. Unlike the previous Plac8 deficient models displaying increased adipose tissue and body weights, our male Plac8 knockout mice showed rather lower body weight than sex-matched littermate controls, though the only difference between these two mouse models is genetic context. Differently from the previously constructed embryonic stem cell-derived Plac8 knockout mouse that contains a neomycin resistance cassette, this knockout mouse model is free from a negative selection marker or other external insertions, which will be useful in future studies aimed at elucidating the multi-functional and physiological roles of PLAC8 in various diseases, without interference from exogenous foreign DNA.

• Parasites, Hosts and Diseases
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• v.60 no.2
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• pp.117-126
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• 2022

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.8
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• pp.1179-1187
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• 2001

In fish both humoral and cell mediated immune responses have been reported whereas antibodies recognizing specific cellular populations have not yet been developed except for ones recognizing surface Ig molecules on B lymphocytes. Our aim was to develop and characterize monoclonal antibodies (Mabs) specific for the immune-related cells. Mabs were produced by fusion of myeloma cells (SP2/0) with Balb/c mouse spleen cells previously sensitized against Israeli carp (I. carp) kidney mononuclear cells. We obtained 44 Mabs positively reacting with I. carp kidney mononuclear cells and partially characterized 7 Mabs in the morphological and mitogen-based proliferative aspects. Fluorescence-activated cell sorter (FACS) analysis against I. carp kidney cells by using 7 different Mabs showed 80.3% for ICK 17-4, 65.1% for ICK 2-3, 64.1% for ICK 25-1, 67.5% for lCK 22-1, 70.8% for ICK 16-2, 76.8% for ICK 13-2, 79.7% for ICK II-I. Panning method was used for the isolation of Mabs specific mononuclear carp spleen cells followed by Wright's stain. The stained cell populations were identified as monocytes (ICK 17-4, ICK 2-3, ICK 25-1, ICK 22-1 and ICK 16-2), lymphocytes (ICK 11-1), and a mixed cell population of monocytes and lymphocytes (ICK 13-2). In cell proliferation assay, monocytes purified by ICK 17-4, 2-3 and 22-1 efficiently responded to Con A and PHA, while ones separated by ICK 25-1 did not react with any mitogens. Lymphocytes isolated by ICK 11-1, though it is not known whether they are T or B cells, were more responsive to Con A than PHA or LPS, suggesting that fish immune cells are somewhat different from mammalian cells in responding to mammalian T or B cell mitogens.