• Journal of Ginseng Research
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• v.33 no.3
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• pp.177-182
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• 2009

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

• Molecules and Cells
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• v.20 no.2
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• pp.167-172
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• 2005

Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-${\gamma}$ in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing mechanism requires binding of a 4-component cytosolic inhibitor complex, IFN-gamma-activated inhibitor of translation (GAIT), to a defined structural element (GAIT element) in the Cp 3'-UTR. Translational silencing of Cp mRNA requires the essential proteins of mRNA circularization, suggesting that the translational inhibition requires end-to-end mRNA closure. These studies describe a new mechanism of translational control, and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.1
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• pp.73-89
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• 2009

Objectives : This study was carried out to investigate the effects of Polygonum cuspidatum extract on several skin functions including inflammation and wrinkle formation. Methods : To investigate in vitro anti-oxidant activity assay, ethanol extracts of medicinal plants tested by DPPH method. In the next experiment, to investigate anti-inflammatory test, the RAW 264.7 macrophage cells was cultured using DMEM including the 10% FBS. To study anti-allergic effect, we blended cultured Human Mast Cells(HMC-1), and then observe $TNF-{\alpha}$, IL-8 by ELISA Results : Polygonum Cuspidatum extract has the effects of anti-inflammation and anti-allergy, which may be due to its inhibitory potential on the macrophage activation. Furthermore, Polygonum Cuspidatum extract has the anti-wrinkle effects through the inhibitory potential on the collagnease, elastase and gelatinase activities. Conclusions : The above results suggest that Polygonum Cuspidatum extract could be applicable for improvement of several skin functions.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.4 no.1
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• pp.23-42
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• 1991

This study were done to know the effects of Dangkiyeumja on the in vivo and in vitro immune responses of mice. The recipes of Dangkiyeumja used in this study enhanced such, cellular functions of immunocytes as phagocytic capacity of macrophages, rossett-eforming abilities of splenocytes and metabolic activities of lymphocytes, However, the same recipes decreased the formation of such reactive oxygen intermediates(ROI) as superoxide and hydrogenperoxide from the macrophages. The effects of the same recipes on the in vim immune responses was suppressive on the cellular immune response(CIR)measured by delayed-type hypersensitivity against dinitrofluorobenzene and mildly enhancing for the humoral immune response measured by antibody production against sheep red blood cells. The results of this study could be summarized as follow: 1. Administration of Dangkiyeumja enhanced the phagocytic activity of the murine macrophage. 2. Administration of Dangkiyeumja decreased the formation of ROI in the murine macrophage 3. Administration of Dangkiyeumja increased the number of the splenic rotte forming cells in the mouse. 4. Administration of DangKiyeumja did not effect the antibody production against sheep red blood cells. 5. Administration of Dangkiyeumja depressed the delayed-type hypersenitivity against dinitrofluoro benzene in the mouse. The result of this study suggest that Dangkiyeumja could ameliorate the hypersensitivity reactions by reducing the formation of ROI and decreasing the CIR without affecting the other functions of immunocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.111-118
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• 2021

27-Hydroxycholesterol (27OHChol) exhibits agonistic activity for liver X receptors (LXRs). To determine roles of the LXR agonistic activity in macrophage gene expression, we investigated the effects of LXR inhibition on the 27OHChol-induced genes. Treatment of human THP-1 cells with GSK 2033, a potent cell-active LXR antagonist, results in complete inhibition in the transcription of LXR target genes (such as LXRα and ABCA1) induced by 27OHChol or a synthetic LXR ligand TO 901317. Whereas expression of CCL2 and CCL4 remains unaffected by GSK 2033, TNF-α expression is further induced and 27OHChol-induced CCL3 and CXCL8 genes are suppressed at both the transcriptional and protein translation levels in the presence of GSK 2033. This LXR antagonist downregulates transcript levels and surface expression of CD163 and CD206 and suppresses the transcription of CD14, CD80, and CD86 genes without downregulating their surface levels. GSK 2033 alone had no effect on the basal expression levels of the aforementioned genes. Collectively, these results indicate that LXR inhibition leads to differential regulation of 27-hydroxycholesterol-induced genes in macrophages. We propose that 27OHChol induces gene expression and modulates macrophage functions via LXR-dependent and -independent mechanisms.

• Journal of Periodontal and Implant Science
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• v.52 no.1
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• pp.28-38
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• 2022

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

• Journal of Ginseng Research
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• v.27 no.3
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• pp.115-119
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• 2003

There has been continuing interest in the development of synthetic and natural compounds that modify the immune response particularly for the treatment of AIDS and cancer. During the past fifty years, numerous scientific studies have been published on ginseng. Modem human studies have investigated preventive effect of ginseng on several kinds of cancer, its long term immunological effect on HIV patients, its effect on cell mediated immune functions in healthy volunteers. Similarly non clinical studies on animal model system have studied the chemopreventive action of ginseng on cancer and immunological properties of ginseng. The precise mechanism of action of ginseng, however, not clearly understood. Considering its wide-ranging therapeutic effects, this study is being undertaken to elucidate the general mode of action of ginseng, especially to test our hypothesis that its biological action may be mediated by the immune system.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1737-1744
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• 2012

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine which plays roles in inflammation, immune responses and cancer development. It assists macrophages in carrying out functions like phagocytosis, adherence and motility. Of late, MIF is implicated in almost all stages of neoplasia and expression is a feature of most types of cancer. The presence of MIF in almost all tumors and all stages of cancer makes it an interesting candidate for cancer therapy. This review explores the roles of MIF in neoplasia.

• Genomics & Informatics
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• v.4 no.2
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• pp.57-64
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• 2006

We identified differentially expressed genes in RAW264.7 cells in response to single and double ligand treatments (LPS, $IFN{\gamma}$, 2MA, LPS plus $IFN{\gamma}$, and LPS plus 2MA). The majority of the regulated transcripts responded additively to dual ligand treatment. However, a significant fraction responded in a non-additive fashion. Several cytokines showing non-additive transcriptional responses to dual ligand treatment also showed non-additive protein production/secretion responses in separately performed experiments. Many of the genes with non-additive responses to LPS plus 2MA showed enhanced responses and encoded pro-inflammatory proteins. LPS plus $IFN{\gamma}$ appeared to induce both non-additive enhancement and non-additive attenuation of gene expression. The affected genes were associated with a variety of biological functions. These experiments reveal both dependent and independent regulatory pathways and point out the specific nature of the regulatory interactions.

• Molecules and Cells
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• v.38 no.10
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• pp.886-894
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• 2015

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.