• Parasites, Hosts and Diseases
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• v.28 no.2
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• pp.91-100
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• 1990

Paragonimus westermani is a tissue migrating parasite in the early stage until arriving at lung, and most of the parasites spend their life spans there. Considerable immune responses including activation of macrophages are taken place during the residence of parasites in the host. However, concerning the immunologic defense mechanisms of the host against this parasite, only a few document is available so far. In this study, the cytotoxic effect of peritoneal macrophages under the presence of antibody and/or complement against metacercariae of F. westermani was investigated in vitro. Metacercarlae were collected from the crayfish, Cambaroides similis and hatched out in Tyrode solution (pH 7.4). Plastic adherent cells from normal or infected rat (Wistar) peritoneal exudates were used as experimental macrophages. Polyclonal antibodies were obtained from infected rats and a cat. Cat IgG was fractioned with ion exchange chromatography. Fresh rabbit complement was used according to experimental scheme. Various combinations of peritoneal macrophages, normal or infected rat serum, complement and cat IgG were incubated at $36^{\circ}C$ in 5% $CO_2$ incubator for 6, 14, 24 and 48 hours. The results obtained were as follows: 1. P. westermani infection activated peritoneal macrophages non-specifically and this activation induced increases of cell adherence and cytotoxicity on metacercariae. 2. In the presence of infected rat serum the antibody.dependent cell-mediated cytotoxicity of peritoneal macrophages on metacercariae was significantly increased and showed a peak at 6-hour incubation. But the cytotoxic effect was markedly reduced after inactivation of complement and heat.labile IgE antibody by the heating of infected serum at 56$^{\circ}C$ for 30 minutes. 3. The highest cytotoxic effect (100%) of concomitant incubation with IgG and complement showed 24 hours after incubation, although cell adherence was relatively low at 6-hour incubation and 0% at 24-hour incubation. 4. Coordinative functions of complement with serum and IgG were effective in cell adherence and in cytotoxicity, but it is not clear the independent role of complement on the macrophage- mediated cytotoxicity in this study- With these results it is assumed that P. westermani infection can induce the non-specific activation of peritoneal macrophages, and strum antibodies including IgE antibody might enhance the cytotoxicity by macrophages,

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.12-29
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• 2006

Background and Aims : Even though various strategies for cancer treatment have advanced with the remarkable development of genomic information and technology, it is far from giving relief to cancer patients. Recently there is accumulating evidence that the immune system is closely connected to anti-tumor defense mechanisms in a multistage process. This includes tumorigenesis, invasion, growth and metastasis. Cordyceps Militaris, a well-known oriental herbal medicine, is a parasitic fungus that has been used as an immune enhancing agent for a long period of time. However, little is known about the cancer-related immunomodulatory effects and anti-tumor activities. In the present study, we aimed to investigate the effects of Cordyceps Militaris extract (CME) on immune modulating and anti-tumor activity. Materials and Methods : To elucidate the effects of CME on macrophage and natural killer (NK) cell activity, we analyzed nitric oxide (NO) production, NK cytotoxicity and gene expression of cytokines related with macrophages and NK cell activity. Results and Conclusions : CME activated and promoted macrophage production of NO. It also enhanced gene expression of IL-1 and iNOS in RAW 264.7 cells. CME promoted cytotoxicity of NK cells against YAC-1 cells and enhanced NK cell related gene expression such as IL-1, IL-2, IL-12, iNOS, IFN-${\gamma}$ and　TNF-${\alpha}$ in mice splenocytes. It also Promoted protein expression of IL-10, IL-12, IFN-${\gamma}$ and TNF-${\alpha}$ in mice splenocytes and inhibited lung tumor metastasis induced by CT-26 cell line compared with the control group. From these results, it could be concluded that CME is an effective herbal drug for modulating the immune system and anti-cancer treatment by promoting macrophage and NK cell activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.11
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• pp.1521-1527
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• 2012

Medicinal herbs have long been used as a remedy for diverse diseases in Asia owing to their various pharmacological effect. In this study, the immuno-enhancing activity of medicinal herbs was investigated using macrophage cell lines. Specifically, we examined the effects of extracts of twelve medicinal herbs on nitric oxide (NO) production in RAW 264.7 cells, and selected five that were highly effective (Glycyrrhiza glabra, Rehmannia glutinosa, Angelica gigas, Platycodon grandflorum, and Actinidia polygama) for further immune related studies. The effects of extracts from five theses medicinal herbs, which were mainly composed of polysaccharides and proteins on the production of immune-related cytokines in the RAW 264.7 macrophage cell line and the Molt-4 T cell line were investigated. The extracts of all investigated medicinal herbs increased the production of NO and cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1beta (IL-$1{\beta}$), interleukin-6 (IL-6) and interleukin-10 (IL-10). Additionally, they slightly increased the proliferation of T-cells when compared to the control. Overall, the result of this study suggests that the five medicinal herb extracts investigated herein are useful natural immune enhancing agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1671-1676
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• 2012

In this study, the immuno-enhancing activity of seed extracts were studied on the macrophage cell lines. We examined the effect of nine seed extracts on nitric oxide (NO) production in RAW 264.7 cells and selected four highly-effective seed candidates (Fagopyrum esculentum, Taraxacum platycarpum, Impatiens balsamina, Helianthus annuus) for further immune-related studies. The effects of the four seed extracts on the production of immune-related cytokines in the RAW 264.7 macrophage cell line and proliferation of Molt-4 as a T cell line were investigated. The secretion of NO from the RAW 264.7 cells was increased up to 39 ${\mu}M$ by adding the seed extracts (25 ${\mu}g/mL$) compared to the control. Also, the secretion of tumor necrosis factor-alpha (TNF-${\alpha}$) was also increased up to 32 times by adding the seed extracts (25 ${\mu}g/mL$). Secretion of cytokines such as interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6), and interleukin-10 (IL-10) was also increased and induced the proliferation of T cells compared to the control. In conclusion, these results suggest that four seed extracts provide beneficial immuno-enhancing effects for human health.

• Proceedings of the Botanical Society of Korea Conference
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• 1985.08b
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• pp.23-33
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• 1985

Plant cell culture is emerging to express bioactive foreign proteins because it has several advantages in that it is safe, economical, genetically stable and eukaryotic expression system comparing with other expression systems. However several limitations such as slow growth rate, low expression level and lack of well established down stream process need to be answered. As a preliminary approach to produce the immunologically interested molecules through the plant cell culture, we tested if granulocyte-macrophage colony stimulating factors (GM-CSFs) from both murine (mGM-CSF) and human (hGM-CSF) are produced as a biologically active form through plant cell culture. The murine and human GM-CSF genes were cloned into the plant expression vector, pBI121, and Ti-plasmid mediated transformation of tobacco leaves was conducted using Agrobacterium tumefaciens harboring both recombinant GM-CSF (rGM-CSF) genes. Cell suspension culture was established from the leaf-derived calli of transgenic tobacco plant. Northern blot analysis indicated the expression of the introduced mGM-CSF gene in both transgenic plant and cell suspension cultures. In addition, the biological activities of both murine and human GM-CSF from plant cell culture were confirmed by measuring the proliferation of the GM-CSF dependent FDC-PI and TF-1 cells, respectively.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.635-647
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• 1995

Human polymorphonuclear leukocytes(PMN) constitute a first line of defense against all forms of injury and microbial challenge, which share a common cell lineage with macrophage. Microbial component LPS activates macrophages to produce IL-1, MIP-1${\alpha}$, -1${\beta}$, TNF-${\alpha}$ and IL-6, etc. Those cytokines have autocrine function to the macrophages, and paracrine function to other cell such as PMN and affect them to produce some biological functions. Having a responsive homogeneous cell line, HL-60, offers us the possibility of studying extensively on the function of PMN, which were not possible previously with peripheral PMN, due to the short-lived nature and difficulty of getting a purified PMN. In the present study, I performed MIP-1 receptor binding assay using HL-60 cell and human peripheral PMN. Also, in vitro antimicrobial assay was performed using differentiated or undifferentiated HL-60 cell. Differentiation was induced by treatment with 500 M of $N^6,O^2-dibutyryl$ adenosine 3'5' cyclic monophosphate(dbcAMP) (PMN-like cell), or 20ng/ml of 12-O-tetradecanoylphorbol-13-acetate(TPA) (macrophage/monocyte-like cell). Receptors for MIP-1${\alpha}$ were identified on dbcAMP-treated HL-60 as well as peripheral PMN. However, bound radioactive MIP-1${\alpha}$ on differentiated HL-60 was much higher than that of peripheral PMN, which suggest receptor number of differentiated HL-60 cell is higher than that of peripheral PMN. Although both of TPA and dbcAMP treatment significantly enhanced antimicrobial action of HL-60 cell, dbcAMP-treated cell(PMN-like HL-60) killed S.aureus more effectively in this experiment. TPA or dbcAMP treatment significantly enhanced antimicrobial action of undifferentiated HL-60 cell. MIP-1${\alpha}$ further increased enhancing effect of TPA or dbcAMP. IL-1${\alpha}$, however, increased only dbcAMP-induced enhancing effect of antimicrobial action of HL-60 cell. These results suggest that differentiated HL-60 cell could replace peripheral PMN in analysis of various biological functions of cytokines on PMN cell.

• Korean Journal of Medicinal Crop Science
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• v.15 no.5
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• pp.324-328
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• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• Journal of Korean Biological Nursing Science
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• v.17 no.4
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• pp.341-347
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• 2015

Purpose: Chrysanthemum indicum (CHI) has been used for edible and medical purposes for a long time in Korea. The purpose of this study was to evaluate the anti-inflammatory effects of CHI water extract in lipopolysaccharides (LPS)-induced RAW 264.7 macrophage cells. Methods: To investigate the anti-inflammatory effects on LPS-induced RAW 264.7 macrophage cells, CHI extract as a whole plant was used in this study. RAW 264.7 cells were treated with various concentrations of CHI extract (1, 10, and $100{\mu}g/mL$). After that Nitric Oxide (NO), inducible nitric oxide synthase (iNOS), interleukin (IL)-$1{\beta}$, cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$) expression level were measured. Results: CHI extract significantly suppressed the LPS-induced NO production and decreased the level of iNOS, IL-$1{\beta}$, COX-2 messenger ribonucleic acid (mRNA) expression and also the down regulation of $PGE_2$ expression in a dose-dependent manner. Conclusion: The present study suggested that CHI extract can be substituted for anti-inflammatory drugs and provide a safe and effective non pharmacological therapeutic approach.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.97-101
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• 2011

Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. In this study we investigated the role of polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense as an immune-modulator. PA was evaluated as inhibitors of some macrophage functions involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-$1{\beta}$) and tumor necrosis factor-alpha (TNF-$\alpha$), and nitric oxide (NO) in murine macrophage cell line, RAW264.7. There was no effect on cytokine production of macrophages by PA itself. However, PA inhibited lipopolysaccharide (LPS)-induced IL-$1{\beta}$ and TNF-$\alpha$ production by macrophages at a dose dependent manner. PA also suppressed the NO production of macrophages by LPS. LPS-induced NF-${\kappa}B$ activity was decreased by treatment of PA. Therefore, these results suggest that PA has anti-inflammatory effect by inhibiting the NF-${\kappa}B$ activation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.3
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• pp.362-370
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• 1995

Human plasma low density lipoprotein(LDL) is the main carrier for cholesterol, and recent studies suggest the normal LDL can be readily oxidized by free radical and not interact with LDL receptor. Lipoprotein pariticles are consisted of lipid andprotein, and fatty acids of lipoproteins are prone to oxidation. LDL particles readily undergo oxidative modification by copper. From the results, oxidized LDL altered its biological properties. A marked increase in the electrophoretic mobility of LDl on agarose gel indicated that negative surface charge of the LDL particles was increased. Also, the results from the HPLC showed that oxidized LDL was degraded into several polypeptides nonenzymatically. Degradation tests which measured the amount of 5-IAF labelled oxidized LDL were carried out by monocyte and hepatocyte cell culture. Hepatocyte cell culture of modified LDL did not show consistent pattern. However, binding rate of modified LDL with HMDM(human monocyte derived macrophage) was enhanced with oxidation, but was retarded by addition of antioxidants(hyaluronic acid, vitamin A, vitamin E). Also comparisons of oxidized-LDL, acetyl-LDL and MDA-LDL showed significant differences in the chemical properteis and binding affinity to HMDM. Thus, modificaition of normal LDL altered its biological properties.