• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.898-904
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• 2003

Pellinus linteus has been used for the prevention of cancer traditionally. There are three origins of Pellinus linteus, Korea, China and Cambodia. However, their immunological activities were not evlauated comparatively. Thus, this study was done to evaluate immunomodulatory effects of Phellinus linteus(PL) from Korea, china and cambodia, We confirmed PL showed two major protein bands, 50 kDa and 80 kDa by protein analysis. These PL effectively upregulated the expressions of IL-2 at 10 ug/ml and GM-CSF, IL-4, IL-10, IL-12(p35), IL-12(p40), IL-18, IFN-r in all concentrations. However, Korea-PL upregulated the expression of IL-12 more effectively than the other PLs. It intended to increase NO with no significance. Those results indicate Phellinus linteus had cytokine modulating effect

• IMMUNE NETWORK
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• v.21 no.1
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• pp.3.1-3.16
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• 2021

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.83-90
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• 2015

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.8
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• pp.1098-1104
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• 2005

The trial was carried out on twenty-one Friesian cows at the end of eight months gestation, nine multiparous and twelve primiparous; allocated into three groups (1 control, 2 and 3 experimental). The same diet was administred to all three groups before partum (12.8 kg DM/head/day) and after partum (18.8 kg DM/head/day). The cows in groups 2 and 3 received two different daily quantities of amino-acid chelated chromium (0.6 and 1.2 mg Cr/kg DM) from 4 weeks prior to presumed parturition to 6 weeks after. The milk yield control was carried out at 15, 30, 42 and 60 days. All animals were immunised two weeks prior to the presumed parturition and two weeks after with the following antigens: ovalbumin and brucellergene. Blood samples were collected weekly to monitor humoral and cell-mediated immune responses. When analysing the results of antibody immunity (ovalbumin) in the sixth blood collection both treated groups significantly increased compared to group 1 (0.5230 and 0.4536 vs. 0.1812 OD; p<0.05). The results of the cell-mediated immune response (brucellergene) had significant differences (p<0.10) in correspondence to the third (between group 2 and control) and the fifth (between groups 3 and 2) blood collection. Significant differences in fat corrected milk were observed at 42 days between group 3 and the other two groups (31.01 vs. 26.99 and 28.66 kg/d, p<0.05) and at 60 days between group 3 and control (30.88 vs. 26.69 kg/d, p<0.05). Before partum and at partum a positive immune response was obtained with a lower dose of chromium. After partum a positive immune response, anti-OVA indicator, was obtained with the higher dose of chromium while, $\gamma$-IFN indicator, with the lower dose. A significant increase of the milk yield resulted at both 42 and 60 days with the highest level of chromium.

• Journal of Microbiology and Biotechnology
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• v.17 no.9
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• pp.1513-1520
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• 2007

[ ${\beta}$ ]-1,3-Glucans enhance immune reactions such as antitumor, antibacterial, antiviral, anticoagulatory, and wound healing activities. ${\beta}$-1,3-Glucans have various functions depending on the molecular weight, degree of branching, conformation, water solubility, and intermolecular association. The molecular weight of the soluble glucan was about 15,000 as determined by a high-performance size exclusion chromatography. From the infrared (IR) and $^{13}C$ NMR analytical data, the purified soluble glucan was found to exclusively consist of ${\beta}$-D-glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the soluble ${\beta}$-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and confirmed the following activities. IFN-$_{\gamma}$ and each cytokines were induced in the spleens and thymus of mice treated with soluble ${\beta}$-1,3-glucan. Adjuvant effect was observed on antibody production. Nitric oxide was synthesized in monocytic cell lines treated with ${\beta}$-1,3-glucan. The cytotoxic and antitumor effects were observed on various cancer cell lines and ICR mice. These results strongly suggested that this soluble ${\beta}$-1,3-glucan could be a good candidate for an immune-modulating agent.

• Natural Product Sciences
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• v.24 no.1
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• pp.21-27
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• 2018

Psoriasis is an auto-immune skin disease, which is characterized by the excessive generation of plaques on the skin with typically a long-lasting red, itchy and scaly symptoms. Imiquimod, which has been used for the treatment of external genital warts, actinic keratosis, and superficial basal cell carcinoma, induced of psoriasis-like skin disorders with skin erythema and thickness in mice. In the present study, we tried to find the bioactive herbal extract against imiquimod-induced psoriasis-like skin disorder in mice. During the searching of the herbal extract with anti-psoriatic effect, the ethanolic extract of Cnidium officinale ameliorated imiquimod-induced psoriasis-like skin disorder in mice. The morphological evaluation, H&E staining and Psoriasis Area and Severity Index (PASI) score showed that ear and back thickness, and erythema induced by imiquimod were significantly reversed after the treatment of the cream of the ethanolic extract of C. officinale. The overexpressed myeloperoxidase (MPO) and keratin 6A levels were decreased by the treatment of C. officinale cream. Also, $IFN-{\gamma}$, c-fos and $I{\kappa}B-{\alpha}$ mRNA levels, which are related to the progression of psoriasis, were reduced by C. officinale cream. Thus, the ethanolic extract of C. officinale ameliorated psoriasis-like skin disorder induced by imiquimod and might be the therapeutic agent for psoriasis.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.340-348
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• 2020

This study was conducted to evaluate the immunomodulatory effects of red doraji (Platycodon grandiflorum, RD) prepared by repeated steaming and drying process in the immune-suppressed mice induced by pre (RD-A) or post-treatment (RD-B) with cyclophosphamide. The immune-stimulating effects of ethanol RD extract in in vivo at 150 (RD-1) and 300 mg/kg body weight (RD-2) for RD-A and RD-B groups were measured and compared to the NC group supplied with distilled water only or positive control group. After 14 days of oral supplement, serum IgA, IgG, and cytokine levels, splenocytes proliferation rate, NK cell activity, and gene expression of cytokines were measured as immune related biomarkers. Serum IgA, IgG, IL-1β, and IL-12 levels increased in both RD-A and RD-B groups while serum TNF-α level decreased in RD-A group compared to the NC group. Splenocytes proliferation rate, NK cell activity, and cytokine (IL-1β, IL-6, IFN-γ) expression levels were also improved by RD supplement in the both groups. The RD showed more significant immunomodulatory effects at higher dose (RD-2) rather than the lower dose (RD-1). Thus, RD has an immune efficacy in a dose dependent manner and can be used as an immune stimulating source to improve immunity.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.493-499
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• 2023

In this study we evaluated the immune-enhancing effects of β-glucan, the main component of Euglena gracilis (Euglena), and Euglena on inflammatory factor expression in RAW264.7 macrophages and ICR mice with cyclophosphamide-induced immunosuppression. Macrophages were treated with β-glucan or Euglena for 48 h. The β-glucan and Euglena groups exhibited higher levels of inducible nitric oxide synthase, nitric oxide, and tumor necrosis factor (TNF)-α than the control (vehicle alone) group. Animals were fed saline and β-glucan (400 mg/kg body weight (B.W.)) or Euglena (400 or 800 mg/kg B.W.) for 19 days, and on days 17-19, cyclophosphamide (CCP, 80 mg/kg B.W.) was administered to induce immunosuppression in the ICR mouse model. CCP reduced the body weight, spleen index, and cytokine expression of the mice. To measure cytokine and receptor expression, splenocytes were treated with concanavalin A (ConA) or lipopolysaccharide (LPS) as a mitogen for 24 h. In vivo, ConA stimulation significantly upregulated the expression of interferon (IFN)-γ, interleukin (IL)-10, IL-12 receptor β1, IL-1β, and IL-2 in splenocytes from the β-glucan- or Euglena-treated groups compared with those in the splenocytes from the CCP-treated group; LPS stimulation increased the levels of the cytokines TNF-α, IL-1β, and IL-6 in splenocytes from the β-glucan- or Euglena- treated groups compared with those from the CCP-treated group, but most of these differences were not significant. These results demonstrate the effect of Euglena in ameliorating macrophages and immunosuppression in CCP-treated mice. Thus, Euglena has the potential to enhance macrophage- and splenocyte- mediated immune-stimulating responses.