• Korean Journal of Veterinary Research
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• v.53 no.4
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• pp.225-230
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• 2013

To better understand the role of macrophages in early stages of experimental autoimmune myocarditis (EAM), we compared the expression of inducible nitric oxide synthase (iNOS) and arginase-1, markers for classically activated M1 and alternatively activated M2 macrophages, respectively, in the hearts of EAM-affected and control rats. Immunohistochemical evidence revealed that both iNOS-positive and arginase 1-positive macrophages were found in EAM lesions, while some cells were co-localized with both markers. This finding suggests that the increased level of arginase-1, which is partly from M2 macrophages, contributes to the modulation of EAM, possibly through the reduction of nitric oxide in the lesion.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.367-371
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• 2006

Phellinus pini (Hymenocaetaceae) has been used for the immunomodulating activity hypolipidemic effect, gastric cancer non-insulin dependant diabetes, diarrhea, and menstrual irregularity. From the screening of each fraction for the inhibitory activity of NO production in lipopolysaccaride (LPS) activated RAW 264.7 cells, methanol extract of Phellinus pini and hexane soluble fraction exhibited inhibition of NO production compared with LPS control without toxicity. The hexane soluble fraction showed dose dependent inhibition of NO production. According to activity guided fractionation, the active hexane fr. was repeatedly chromatographed over silica gel, ergosta-4,6,8(14),22- tetraen-3-one was isolated. The compound inhibited NOS activation (IC$_{50}$ = 29.7 uM) and NO production of activated macrophage at 30 uM.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.243-247
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• 2012

Recent studies suggest that immunization with autologous dendritic cells (DCs) results in protective immunity and rejection of established tumors in various human malignancies. The purpose of this study is to determine whether DCs are generated from peripheral blood mononuclear cells (PBMNs) by using cytokines such as F1t-3 ligand (FL), granulocyte macrophage-colony stimulating factor (GM-CSF), IL-4, and TNF-${\alpha}$, and whether cytotoxic T cells activated against the thyroid cancer tissues by the DCs. Peripheral blood was obtained from 2 patients with thyroid cancer. DCs were established from PBMNs by culturing in the presence of FL, GM-CSF, IL-4, and TNF-${\alpha}$ for 14 days. At day 14, the differentiated DCs was analyzed morphologically. The immunophenotypic features of DCs such as CDla, CD83, and CD86 were analyzed by immunofluorelescence microscopy. At day 18, DCs and T cells were incubated with thyroid cancer tissues or normal thyroid tissues for additional 4 days, respectively. DCs generated from the PBMNs showed the typical morphology of DCs. Activated cytotoxic T lymphocytes (CTLs) were observed also. DCs and the CTLs were attached to the cancer tissues on scanning electron microscope. The DCs activated the CTLs, which able to specifically attack the thyroid cancer. This study provides morphologic evidence that the coculture of T cells/cancer tissues activated the T cells and differentiated CTLs. The CTLs tightly adhered to cancer tissues and lysed cancer tissues vigorously. Therefore DCs could be used as potential vaccines in the immunotherapy.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.293-298
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• 2009

Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-$\alpha$, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-$\alpha$ mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.

• The Korean Journal of Food And Nutrition
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• v.19 no.2
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• pp.176-182
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• 2006

Sorghum bicolor L. Moench(Sorghum, Su-Su) is a major cereal food crop used in many parts of the world. It is used as a human food resource and folk medicines in Asia and Africa. The stem of sorghum has been used as a digestive aid and an anti-diarrheal agent. Sorghum hybrids contain high levels of diverse phenolic compounds that may provide health benefits. High levels of polyflavanols, anthocyanins, phenolic acids, and other antioxidant compounds have been reported in sorghums, which have also been shown to possess various biological activities such as anti-mutagenic, anti-carcinogenic, and HMG-CoA reductase inhibitory activities. In an in vitro experiment, we examined mice splenocyte proliferation and production of three types of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by peritoneal macrophages cultured with ethanol and water extracts of Sorghum bicolor L. Moench. A single cell suspension of splenocytes was prepared and the cell proliferation of the splenocytes was examined by MTT assay. The splenocyte proliferation was increased when water extracts of Sorghum bicolor L. Moench were used as supplements in all concentrations investigated. The production of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by activated peritoneal macrophage was detected by ELISA using the cytokine kit. $IL-1{\beta},\;IL-6,\;and\;TNF-{\alpha}$ production by activated macrophages were increased by supplementation with Sorghum bicolor L. Moench water extracts. This study suggests that supplementation of with Sorghum bicolor L. Moench water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing the cytokine production by activated macrophages in vitro.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.675-682
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• 2022

Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.960-966
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• 2003

Macrophages play an important role in host defenses by killing tumors and virus infections and producing secretory products. High mannuronic acid (HMA) containing alginate was examined to determine the mechanisms by which HMA-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macro phages to resist infection with HSV-1 or to inhibit the growth of tumor cells was assessed following treatment with HMA alginate in the presence of either antibodies to various cytokines or inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-$\alpha$/$\beta$ were able to abrogate the protective effects of HMA alginate in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-$\beta$. In contrast, anti-TNF-$\alpha$, anti-IFN and inhibitors of nitric oxide and reactive oxygen species were all able to partially abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. These results indicate that the HMA-induced intrinsic antiviral and extrinsic cytotoxic activites are mediated by different mechanisms.

• Molecules and Cells
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• v.23 no.2
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• pp.198-206
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• 2007

Hydroquinone is a toxic compound and a major benzene metabolite. We report that it strongly inhibits the activation of macrophages and associated cells. Thus, it suppressed the production of proinflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-3, IL-6, IL-10, IL-12p40, IL-23], secretion of toxic molecules [nitric oxide (NO) and reactive oxygen species (ROS)] and the activation and expression of CD29 as judged by cell-cell adhesion and surface staining experiments. The inhibition was due to the induction of heme oxygenase (HO)-1 in LPS-activated macrophages, since blocking HO-1 activity with ZnPP, an HO-1 specific inhibitor, abolished hydroquinone's NO inhibitory activity. In addition, hydroquinone and inhibitors (wortmannin and LY294002) of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway had very similar inhibitory effects on LPS-induced and CD29-mediated macrophage responses, including the phoshorylation of Akt. Therefore, our data suggest that hydroquinone inhibits macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms.

• The Korean Journal of Food And Nutrition
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• v.19 no.3
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• pp.327-331
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• 2006

Zingiber officinale and Hizikia fusiforme(sea weed fusiforme) have long been used for food sources in Korea. The present study was performed to investigate the ex vivo effect of Zingiber officinale and Hizikia fusiforme on NO production in macrophage of mice. Seven to eight week old mices(Balb/c) were fed chew diet ad libitum and water extract of Zingiber officinale and Hizikia fusiforme was administrated orally at two different concentrations (50 and 500 mg/kg B.W.). every other day for two or four weeks NO(nitric oxide) production by activated macrophage was assessed by measuring nitrite, the stable NO metabolite, using Griess reaction assay. NO production were significantly enhanced in Zingiber officinale group at 500 mg/kg B.W. and in Hizikia fusiforme group at 50 mg/kg B.W. compared to the coresponding control groups. In conclusion, this study may suggest that Zingiber officinale and Hizikia fusiforme(sea weed fusiforme) extracts enhance the immune function by regulating NO production in macrophages of mice.