• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6009-6014
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• 2014

Aims: To investigate changes in cellular immune function of patients with lung cancer before and after cytokine-induced killer (CIK) cell therapy and to identify variation effects on overall survival (OS) and progression-free survival (PFS). Materials and Methods:A total of 943 lung cancer patients with immune dysfunction were recruited from January 2002 to January 2010, 532 being allocated to conventional therapy and 411 to CIK therapy after a standard treatment according to the NCCN Clinical Practice Guidelines. All the patients were investigated for cellular immune function before and after therapy every three months. and clinical prognostic outcomes were analyzed. Results: After six courses of treatment, immune function was much improved in patients receiving CIK cells therapy as compared to controls. The percentages of recurrence and/or metastases for patients undergoing CIK cell therapy was 56.2% and 49.1% respectively but 78.6% and 70.3% among controls (p<0.001). The median OS times for CIK cell therapy and control groups were 48 and 36 months respectively. The OS rates at 12, 36, 60, 84 months in CIK treated patients were 97.8%, 66.9%, 27.7%, and 4.1% while they were 92.3%, 44.5%, 9.2%, and 1.5% in controls. OS and PFS were significantly different by log rank test between the two groups and across the three immune improvement classes. Conclusions: The immune function of lung cancer patients was improved by CIK cell therapy, associated with an increase in the OS rate and extension of the time to recurrence and/or metastasis.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.483-489
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• 2002

APA-01, which is an aqueous extract of five Chinese herbs, is a modified formula of Huoxiang-Zhengqi-San. The effect of new herb extract on immune response was investigated. The parameter examined to assess apparent immune response of APA-01 in mice included changes of body weight, relative weight of immune organs, cell proliferation and cytokine gene expression. The body weight and relative weight of immune organs were not significantly changed among the tested groups. In the spleen cell prolijeration assay, APA-01 increased the cell proliferation in a dose-dependent manner. Methotrexate (MTX), an agent of immune suppression, inhibited the spleen cell proliferation (IC/sub 50/: 800㎍/㎖). However, APA-01 significantly inhibited the suppression of mouse spleen cell proliferation. Therefore, it seems that APA-01 has a reducing effect of immune suppression. Immunomodulatory effect of APA-01 was further investigated using reverse transcription polymerase chain reaction (RT-PCR) in mouse spleen cells. In RT-PCR test, APA-01 enhanced the expression of cyclooxygenase-2 (COX-2) mRNA in a dose-dependent manner. In spite of immune suppression by MTX, COX-2 mRNA was induced by co-treatment with APA-01. These results suggest that APA-01 stimulates the proliferation of spleen cells, regulates the expression of COX-2 mRNA, and accelerates the recovery of inhibition of spleen cell proliferation induced by MTX, thus providing the immunological basis for clinical benefit of APA-01.

• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1517-1526
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• 2016

Lactic acid bacteria (LAB) isolated from fermented foods have potential as a treatment for immune-related disorders and the use of LAB has been increasing worldwide. In this study, the differential cytokine regulatory effect was examined with three isolates of lactobacilli strains; namely, Lactobacillus plantarum K55-5 isolated from dairy product, and L. sakei K101 and L. plantarum K8 previously isolated from kimchi (a Korean traditional fermented vegetable). Production of cytokines such as IL-10, IL-12, IFN-γ, and TNF-α was significantly increased in L. sakei K101- and L. plantarum K55-5-treated splenocytes as compared with controls. The oral administration of L. sakei K101 and L. plantarum K55-5 increased cytokine production in the immunosuppressed mouse splenocytes and blood. NK cell cytotoxic activity was also increased in L. sakei K101- and L. plantarum K55-5-fed mice. On the other hand, L. plantarum K8 did not affect cytokine induction in all the experiments performed in this study. The cytokine-inducing effect of L. plantarum K55-5 was significantly increased by lysates of heat-killed bacteria as compared with live, heat-killed, or supernatant of cell lysates. TNF-α production by lipoteichoic acids (LTAs) isolated from the three isolates of lactobacilli was compared, and it was found that K55-5 LTA had a highest cytokine-inducing ability, which was mediated by TLR2-mediated NF-κB and ERK activation. Taken together, our study suggests that L. plantarum K55-5 and L. sakei K101 can be used for the treatment of immunosuppressed disorders.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.15.1-15.16
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• 2022

Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells. To identify cytokine expression profiles, both the THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA or SEB. A total of 21 cytokines were evaluated in the culture supernatants. We observed that stimulation with dsRNA induced cytokine production in both cell types. However, cytokine production was not induced in SEB-stimulated epithelial cells, compared to the macrophages. The synergistic effect of dsRNA and SEB was evaluated observing cytokine level and intracellular phospho-signaling. Fifteen different types were detected in high-dose dsRNA-stimulated epithelial cells, and 12 distinct types were detected in macrophages; those found in macrophages lacked interferon production compared to the epithelial cells. Notably, a synergistic effect of cytokine induction by co-stimulation of dsRNA and SEB was observed mainly in epithelial cells, via activation of most intracellular phosphor-signaling. However, macrophages only showed an accumulative effect. This study showed that the type and severity of cytokine productions from the epithelium or macrophages could be affected by different intensities and a combination of dsRNA and SEB. Further studies with this approach may improve our understanding of the development and exacerbation of airway inflammation and asthma.

• Korean Journal of Pharmacognosy
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• v.41 no.1
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• pp.31-37
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• 2010

The Salvia plebeia R. which is the biennial plant belonging to the Labiatae department, grows naturally in the Korea entire area. Presently, its extract (SPRE) is known to have an anti-inflammation and anti-allergy activity, but there are a few evidences about it. SPRE inhibits pro-inflammatory cytokine such as TNF-$\alpha$ and IL-6 as well as nitric oxide (NO) production in lipopolysaccharide (LPS) treated- macrophages. The co-administration of SPRE during OVA sensitization significantly reduced total IgE levels in mice. The mice who received SPRE co-administered with OVA showed a significant increase in serum OVA-specific IgG2a/b levels. Spleen-cell cultures harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels with a concomitant increase in Th1 cytokine levels only when SPRE co-administered with OVA. These results demonstrate that SPRE can control the LPS-induced inflammatory reaction and prevent antigen-induced Th2 immune responses in mice.

• Journal of Acupuncture Research
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• v.23 no.1
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• pp.121-134
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• 2006

Objectives : This experiment was conducted to evaluate inhibitory effects against hepatic metastasis and promotion of immunocytes by cultivated wild ginseng Herbal Acupuncture. Methods : Colon26-L5 carcinoma cells were injected through hepatic portal vein to induce hepatic metastatic cancer. Changes in weight, morphology of the cancer, histological impressions were evaluated and cytokine level was analyzed to yield immunological changes. Colon26-L5 carcinoma cells were injected through hepatic portal vein to induce hepatic metastatic cancer. Changes in weight, morphology of the cancer, histological impressions were evaluated and cytokine level was analyzed to yield immunological changes. Results : 1. Mice treated with cultivated wild ginseng Herbal Acupuncture reduced metastatic size compared to the control group. 2. No distinctive differences were witnessed between the cancer cells of control and experimental group in histological observation, but experimental group was closer to the normal tissue condition. 3. Observing immunocytes from the spleen of experimental group, T-lymphocytes were significantly increased. 4. Measuring the level of cytokine IL-4 which stimulates Th 2 were significantly increased. These findings strong1y indicate cultivated wild ginseng Herbal Acupuncture enhances immunity to inhibit the growth of cancer and metastasis.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.474-480
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• 1999

The purpose of this study is to define whether Asterina pectinifera Lectin (APL) is effective on the cytokine production. Isolated mRNA from hPBMC (human peripheral blood mononuclear cells) stimulated with APL for various reaction times (1 to 96 hours) was detected by RT-PCR. The intensity of band for IL-1 and $IFN{\gamma}$ mRNA was markedly increased at l hour, and IL-2 mRNA was strongly expressed at 4 hours. The mRNA band of APL-induced IL-2 and $IFN{\gamma}$ was weaker than that of IL-1, IL-6 and $TNF{\alpha}$. The mRNA expression of 4 cytokines (IL-1, IL-2, $IFN{\gamma}$ and $TNF{\alpha}$) was detected up to 48 hours, and that of IL-6 was detected until 72 hours. ELISA was used to look protein secretion of the cytokine gene with IL-1, IL-2 and TNF$\alpha$expressed strongly in RT-PCR. The highest protein secretion was at 4 hours with IL-1, at 8 hours with IL-2 and at 4 hours with $TNF{\alpha}$. These results suggest that APL can induce the production of some cytokines and the immune response from PBMC was done within the first few hours of stimulation with APL.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.366-371
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• 2012

In this present study, we determined whether or not there is an immunoadjuvant effect of ochnaflavone, a biflavone isolated from Lonicera japonica. As an antigenic source, the cell wall (CACW) of Candida albicans, a fungal pathogen, was used. CACW consists of 95% carbohydrate (mannan). In the experiments, BALB/c mice were immunized with emersion forms of CACW combined with or without ochnaflavone (Och) in the presence of IFA containing mineral oil or CACW alone. Then, the amounts of antisera collected from these mice groups were measured by the ELISA method. Data from these experiments showed that CACW combined with Och (CACW/Och/IFA) provoked the production of antisera app. 2.2 or 5 times more than the corresponding CACW/IFA or CACW alone (CACW/DPBS), respectively, in mice (P<0.05). We further examined the immune response type induced by Och. Analysis of the values of the IgG1/IgG2a ratios obtained from IgG isotyping revealed that Och induced Th2-immunity more dominantly than Th1. This finding was confirmed by cytokine profile. CACW/Och/IFA formulation induced IL-4 (Th2-type cytokine) more than IFN${\gamma}$ (Th1-type cytokine) as compared with CACW/IFA and CACW/DPBS formulations (P<0.05). All data combined, Och appears to have an immunoadjuvant activity that may convert Th1 immunity into Th2 immunity.

• Journal of Nutrition and Health
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• v.42 no.3
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• pp.207-212
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• 2009

Codonopsis lanceolatae has been used as one of the traditional remedies as well as food source. However, few studies on their immunomodulating effects have been reported. We previously reported that ex vivo supplementation of Codonopsis lanceolatae water extracts enhanced splenocyte proliferation compared to the control group. In order to elucidate its ex vivo effect, six to seven week old balb/c mice were fed ad libitum on a chow diet and water extracts of Codonopsis lanceolatae were orally administrated every other day for four weeks at two different concentrations (50 and 500 mg/kg B.W). After preparing the single cell suspension, the proliferation of splenocytes was determined by MTT (3- [4,5-dimethylthiazol-2-y] -2,5-diphenyl terazolium bromide) assay. The production of cytokine (IL-1${\beta}$, IL-6, TNF-${\alpha}$), secreted by macrophages stimulated with LPS or not, was detected by ELISA assay using a cytokine kit. After 48 hrs of incubation with the mitogen (ConA or LPS) stimulation, the mice splenocyte proliferation in experimental group was statistically increased at two different concentrations than that in control group. The cytokines production was more significantly enhanced at the lower supplementation (500 mg/kg B.W.) group rather than higher concentration (500 mg/kg B.W.) compared to the control group. The results of this study may suggest that the supplementation of water extract of plant mixture could regulate the immune function by increasing the splenocyte proliferation and enhance the immune function through regulating cytokine production capacity by activated macrophages in mice.