• IMMUNE NETWORK
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• v.10 no.5
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• pp.173-180
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• 2010

Background: APRIL, originally known as a cytokine involved in B cell survival, is now known to regulate the inflammatory activation of macrophages. Although the signal initiated from APRIL has been demonstrated, its role in cellular activation is still not clear due to the presence of BAFF, a closely related member of TNF superfamily, which share same receptors (TACI and BCMA) with APRIL. Methods: Through transfection of siRNA, BAFF-deficient THP-1 cells (human macrophage-like cells) were generated and APRIL-mediated inflammatory activities were tested. The expression patterns of APRIL were also tested in vivo. Results: BAFF-deficient THP-1 cells responded to APRIL-stimulating agents such as monoclonal antibody against APRIL and soluble form of TACI or BCMA. Furthermore, co-incubation of the siBAFF-deficient THP-1 cells with a human B cell line (Ramos) resulted in an activation of THP-1 cells which was dependent on interactions between APRIL and TACI/BCMA. Immunohistochemical analysis of human pathologic samples detected the expression of both APRIL and TACI in macrophage-rich areas. Additionally, human macrophage primary culture expressed APRIL on the cell surface. Conclusion: These observations indicate that APRIL, which is expressed on macrophages in pathologic tissues with chronic inflammation, may mediate activation signals through its interaction with its counterparts via cell-to-cell interaction.

• The Korea Journal of Herbology
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• v.23 no.3
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• pp.103-112
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• 2008

Objectives : This research aimed to study the cytotoxicity and immuno modulating activity of fermented Artemisia argyi Lev. et Vant.(Compositae). Methods : Effect of fermented Artemisiae Argyi Folium extracts, which were fermented by Sacchromyces cerevisiae STV89(AFS), on cell viability, generation of ROS within cells, generation of NO and the level of cytokines($TNF-{\alpha}$ and IL-6) was measured using mouse macrophage RAW 264.7 cell. Results : 1. Result of MTT assay conducted to verify the cytotoxicity of fermented Artemisiae argyi folium extract illustrated that, when fermented Artemisiae argyi folium extract was processed for each concentration, there was no excessive induction of cytoxicity in the RAW 264.7 cell. 2. Fermented Artemisiae Argyi Folium extract increased the generation of H2O2 within RAW 264.7 cell as well as significantly increased inhibition of generation of H2O2 in macrophage induced by LPS. 3. Fermented Artemisiae Argyi Folium extract inhibited generation of NO in RAW 264.7 cell, and significantly inhibited increase in generation of NO of macrophage induced by LPS. 4. Fermented Artemisiae Argyi Folium extract, AFS has significantly reduced the increase in the generation of $TNF-{\alpha}$ above 10 ${\mu}g/mL$. 5. Fermented Artemisiae Argyi Folium extract, AFS has significantly reduced the increase in generation of IL-6 above 50 ${\mu}g/mL$. Conclusions : AFS fermented extract produced from Artemisiae Argyi Flium, have increased generation of ROS and reduced generation of NO in RAW 264.7 cell without excessively inducing cytotoxicity of RAW 264.7 cell. In addition, they displayed significant immuno modulating activities including inhibition of generation of $TNF-{\alpha}$ and IL-6 in macrophage, induced by LPS.

• Journal of Ginseng Research
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• v.15 no.2
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• pp.99-105
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• 1991

This experiment was performed to investigate the effects of ginseng saponin fraction and cyclophosphamide (CY) on the tumor development, the antitumor effect and the tumoricidal activity of mouse macrophage. When mice were treated with saponin or CY following inoculation with Sarcoma 180, tumor development was inhibited and survival ratio increased, and a combination of both treatments further inhibited the tumor development. Tumoricidal activity of macrophage was effectively increased at 10-7% concentration of CY and it was further increased when macrophage was cotreated with saponin and CY. Tumoricidal activity of macrophage was greatest at the third day after inoculating tumor cell. Both saponin and CY increased the chemiluminescence of macrophage, but CY had no effect on releasing TNF, unlike saponin.

• Microbiology and Biotechnology Letters
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• v.27 no.6
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• pp.509-514
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• 1999

Forty seven amylolytic Bifidobacterium strains were isolated on starch-containing agar medium from the faecal samples of the various age groups of Korean. From these amyloytic Bifidobacterium spp., two strains of KFRI 1535, identified temporarily as Bifidobacterium longum, and KFRI 1550, identified as Bifidobacterium breve, showed great macrophage-stimulating activity for the production of tumor necrosis factor-$\alpha$ and inteleukin-6. As the cell concentration increased the cytokine production increased, although in some strains the cytokine levels started to decline over cell concentration increased the cytokine production increased, although in some strains the cytokine levels started to decline over cell concentration of $250\mu\textrm{g}$/ml. the strains which showed high cytokine-stimulating activity generally showed greater production of nitric oxide even though differences were less between strains. Selected Bifidobacterium strains were compared for their fermentation capability in saccharified rice solution and in apple pomace mixture.

• Molecules and Cells
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• v.20 no.2
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• pp.271-279
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• 2005

Although macrophages are an important first line of cellular defense, they are unable to effectively kill phagocytosed C. albicans. To determine the physiological basis of this inability, we investigated the alterations of macrophage proteins caused by C. albicans infection. Since the formation of C. albicans hyphae caused cell death, proteins were prepared 3 h after infection and examined by two-dimensional gel electrophoresis (2-DE). The most prominent changes were in glycolytic enzymes, which could have caused energy depletion of the infected cells. Also changed were proteins involved in maintenance of cellular integrity and NO production. Treatment of the macrophages with either cytochalasin D or taxol did not alter their inability to kill C. albicans. Our results indicate that multiple factors contribute to cell death as the pathogenic form of C. albicans becomes fully active inside macrophage cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5883-5890
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• 2013

Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs). However, the function and expression of SEMA4D in the EOC microenvironment has yet to be clarified in detail. In this study, we confirmed that overexpression of SEMA4D in primary tumors and ascites was related to low differentiation, platinum resistance and a refractory status (P<0.05), while high M2 macrophage count and percentage were evident in EOC patients with advanced FIGO stage and platinum resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The data showed correlations of SEMA4D expression and M2 macrophage counts in primary tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05). In the Cox proportional hazard mode, SEMA4D expression was an independent indicator of overall survival (OS) and progression-free survival (PFS) for EOC patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines (SKOV3, A2780, and SW626) and their supernatants were found than that in a human primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT-PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood monocytes (MOs) tended towards the M2-polarized macrophage phenotype ($CD163^{high}$) in vitro after human recombined soluble SEMA4D protein stimulation. These findings suggest that SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis and could playan important role in promoting tumor dissemination and metastasis in the EOC microenvironment. Thus SEMA4D and its role in macrophage polarization in EOC warrants further study.

• KSBB Journal
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• v.5 no.2
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• pp.113-118
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• 1990

This experiment was carried out to investigate the immuno-regulatory effects of histamine on IL-1 synthesis and Ca2+ uptake in P388Dl macrophage-like cell line. The addition of histamine (10-8-10-3 M) increased IL-1 production in P388D1, cells, in a dose dependent manner, the treatment of EGTA (10-7-10-4M) and Co2+ ion (10-5-10-4M) decreased macrophage-derived IL-1 activity, and the pretreatment of histamine at the peak of 10-4M significantly enhanced Ca2+ uptake to P388Dl Cells. These results suggested that exogenous histamine was effective on IL-1 production from macrophage and the intracellular Ca2+ uptake play a important role in histamine-stimulated IL-1 synthesis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• Preventive Nutrition and Food Science
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• v.11 no.4
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• pp.273-277
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• 2006

Recently, Rhei Rhizoma extracts (RRE) have begun to receive more attention as potential biological response modifiers. In the present study, we studied the antiproliferative effect of RRE on tumor cells and the effect of RRE on macrophage function. A variety of tumor cells and macrophages were treated with RRE at various concentrations. The effect of RRE on cell proliferation was measured by MTT assay and the effect of RRE on the production of nitric oxide (NO) was determined in the macrophage-like cell lines Raw264.7, C6 and peritoneal macrophages (pMQ). RRE inhibited the growth of tumor cells (e.g., B16, HOS). However, the effects of RRE on the production of NO varied with macrophage types. RRE had no effect on C6 cell growth and slightly increased the growth of Raw264.7 cells. In addition, treatment of normal pMQ with RRE enhanced NO production in a concentration-dependent manner, whereas RRE suppressed NO production at $50\;{\mu}g/mL$ in both Raw264.7 and C6 cells. However, RRE suppressed NO production in LPS/IFN-$\gamma$-stimulated C6 cells. Overall, these results suggest that RRE elicits an antiproliferative property and differentially modulates NO production in various macrophages, and have a potential for therapeutic application.

• Natural Product Sciences
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• v.13 no.4
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.