• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.481-486
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• 2013

Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.351-355
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• 2008

Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin, and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on the function of macrophage and splenocyte has not been characterized in detail. In the present study, we examined the effects of prodigiosin for its ability to alter the function of murine macrophage and NK cell, and the proliferation of splenocytes. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-50 ng/ml) were stimulated with LPS/IFN-$\gamma$, pretreatment with prodigiosin resulted in the inhibition of tumoricidal activity of macrophage in a concentration-dependent manner. Tumoricidal activity of NK cell was also inhibited by prodigiosin. Moreover, we found that prodigiosin was able to cause a dose-dependent inhibition of murine lymphocyte responsiveness to Con A and LPS although T-mitogenic response was the more sensitive one. Taken together, the present results point out that prodigiosin has a suppressive effect on the mitogen-induced proliferation of murine lymphocytes and the function of macrophage and NK cell.

• Biomedical Science Letters
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• v.9 no.2
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• pp.85-91
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• 2003

Gentiana scabra var. buergeri (G. scabra) is a herb known to have therapeutic effect in infection diseases. We studied cellular activation and antitoxoplasmosis in macrophages after G. scabra stimulation. Macrophage activation was detected by nitrite production. Macrophages were treated with G. scabra extracted with water or methanol. Maximal nitrite production was detected in macrophages after stimulation of G. scabra extract 0.1 mg/ml. Maximal nitrite concentration was 23.22 0.003 uM/L in macrophages after water extract of G. scabra and was 24.07 1.41 uM/L after methanol extract of G. scabra. Effect of G. scabra in the phagocytic capacity of macrophages was monitored by using PI (percentage of macrophage infected by T gondii) method. The minimum PI (42.5 2.31) was detected in macrophages treated by water extract of G. scabra 0.1 mg/ml before infection of T gondii. We also examined toxoplasmastatic capacity of macrophage using FI (fold increase) method. The minimum FI (4.46 1.16) was shown in macrophages after water extract of G. scabra 0.1 mg/ml pretreatment before infection. Under electron microscope, proliferation of T gondii was inhibited by extract of G. scabra treatment in macrophages and the mitochondrion and lysosomal vacuoles within cells were increased. Taken together, G. scabra extract activates macrophages and induces toxopalsmastatic activity after T gondii infection. It is suggested that G. scabra may be used as a therapeutic drug against toxoplasmosis.

• 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 Applied Biological Chemistry
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• v.64 no.3
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• pp.263-268
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• 2021

7-Hydroxy-4-methylcoumarin (7H-4MC) inhibits hyaluronan production in multiple cell lines and tissue types both in vitro and in vivo. It is a commercially available drug approved for human use, called hymecromone, in European and Asian countries to prevent biliary spasms. Nevertheless, as the pharmacological efficacy of 7H-4MC has not yet been reported in macrophages, this study investigated its anti-inflammatory effects and mechanism of action using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. LPS-induced RAW 264.7 cells were treated with various concentrations of 7H-4MC (62.5, 125, 250, and 500 μM). The application of 7H-4MC significantly reduced nitric oxide and prostaglandin E₂ production without cytotoxic effects. Additionally, 7H-4MC strongly decreased the expression of inducible nitric oxide synthase and cyclooxygenase. Furthermore, 7H-4MC reduced the production of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, 7H-4MC exerted its potent anti-inflammatory actions via the upregulation of IκB-α production, which led to the inhibition of nuclear factor-κB (NF-κB) activity. These results, obtained in macrophage cell lines, suggest that 7H-4MC prevents inflammatory diseases via the NF-κB signaling pathway and that its use could be beneficial for human health. Ultimately, this is the first report describing the anti-inflammatory activity of 7H-4MC in a macrophage cell line.

• The Korean Journal of Food And Nutrition
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• v.35 no.6
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• pp.399-410
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• 2022

To enhance the bioavailability and bioactivities of mixed herbal medicines (RW), they were fermented with lactic-acid bacteria isolated from kimchi into postbiotics (FRW). Then, from the results of the 16s rRNA sequencing analysis, lactic acid bacteria isolated from kimchi were identified to be of two species, namely Lactobacillus sakei and Leuconostoc mesenteroides. The FRW prepared from the RW were extracted using hot water (HW) and 70% EtOH (EtOH) for comparison of their macrophage-stimulating activities. Based on a comparison of the activities of the FRW extracts, nitric oxide (NO) production of HW was significantly higher than that in EtOH. An analysis of the chemical properties of the extracts showed that HW had higher contents of neutral sugar and uronic acid than EtOH as well as contained a large amount of glucose. In addition, crude polysaccharide (CP) was prepared to enhance the macrophage-stimulating activity. The FRW-CP not only secreted immunostimulatory mediators but also increased the expression of immunostimulatory genes (iNOS, TNF-α, MCP-1, and IL-6). The fractionated FRW-CP contained about 90% neutral sugars, and these sugars were mainly composed of glucose, galacturonic acid, and arabinose. Thus, FRW prepared by fermentation of RW with kimchi lactic acid bacteria were found to be immunostimulatory modulators.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.257-265
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• 2023

Kidney ischemia/reperfusion (I/R) injury, a common cause of acute kidney injury (AKI), is associated with the migration of inflammatory cells into the kidney. Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho family of small GTPase, plays an important role in inflammatory cell migration by cytoskeleton rearrangement. Here, we investigated the role of Rac1 on kidney I/R injury and macrophage migration. Male mice were subjected to either 25 min of bilateral ischemia followed by reperfusion (I/R) or a sham operation. Some mice were administrated with either NSC23766, an inhibitor of Rac1, or 0.9% NaCl (vehicle). Kidney damage and Rac1 activity and expression were measured. The migration and lamellipodia formation of RAW264.7 cells, mouse monocyte/macrophage, induced by monocyte chemoattractant protein-1 (MCP-1, a chemokine) were determined using transwell migration assay and phalloidin staining, respectively. In sham-operated kidneys, Rac1 was expressed in tubular cells and interstitial cells. In I/R-injured kidneys, Rac1 expression was decreased in tubule cells in correlation with the damage of tubular cells, whereas Rac1 expression increased in the interstitium in correlation with an increased population of F4/80 cells, monocytes/macrophages. I/R increased Rac1 activity without changing total Rac1 expression in the whole kidney lysates. NSC23766 administration blocked Rac1 activation and protected the kidney against I/R-induced kidney damage and interstitial F4/80 cell increase. NSC23766 suppressed monocyte MCP-1-induced lamellipodia and filopodia formation and migration of RAW 264.7 cells. These results indicate Rac1 inhibition protects the kidney against I/R via inhibition of monocytes/macrophages migration into the kidney.

• Biomolecules & Therapeutics
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• v.7 no.4
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• pp.377-384
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• 1999

Alginates are polysaccharides with gel-forming properties composed of 1,4-linked $\beta$-D-mannuronic acid (M), $\alpha$-L-guluronic acid (G), and alternating (MG) blocks. The M-and the MG-blocks, but not the G-blocks, have been known to be the active components of the alginates in experimental models. In this study, we have examined the ability of high M-alginate to activate immune cells. Alginate induced the macrophage anti-viral activity and the lymphocyte blastogenesis, and enhanced cytotoxicity of natural killer cell. In addition, alginates stimulated the macrophages to induce the production of $H_{2}O_{2}$, whereas alginates had no effect on NO production and suppressed the production of TNF-$\alpha$. These findings suggest that high M-alginate may be modulating various elements of the host immune response.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.1-4
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• 2003

Plants are known as important source in the search for new drugs. The twelve compounds from Viscum album (Loranthaceae), lupeol (1), betulonic acid (2), betulinic acid (3), terminic acid (4), ursolic acid (5), $\beta$-sitosterol (6), $\alpha$-spinasterol (7), oleanolic acid (8), 5-hydroxy-1-(4′-hydoxyphenyl)-7-(4"-hydroxyphenyl)-hepta-1-en-3-on (9), 2′-hydroxy-4′,6′-dimethoxychalcone-4-O-glucoside (10), 2′-hydroxy-4′,6′-dimethoxychalcone-4-O-[apiosyl(l$\longrightarrow$2)]glucoside (11) and syringin (12) were evaluated for their immunomodulatory properties. Compounds 6 and 11 induced the macrophage tumoricidal activity and the lymphocyte blastogenesis. In addition, these compounds stimulated the macrophages to induce the production of TNF-$\alpha$ and NO. These findings suggest that compounds 6 and 11 are modulating various elements of the host immune response.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.498-502
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• 2010

The immune system may play an important role in aging and the changes in the immune status are associated with treatment of various immunomodulators. This study examined the effects of $\beta$-glucans isolated from mushroom fungi, Coriolus versicolor on macrophages functions in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice. When peritoneal macrophages were treated with various concentrations of $\beta$-glucan ($1-100\;{\mu}g/ml$) for 24 hrs, tumoricidal activity, NO production and phagocytic activity were significantly increased in the young mice, whereas there are no effects in the aged mice. These results suggest that $\beta$-glucans has differential effects on the macrophage functions in young and aged mice and age nutrition might need to be considered to select proper immunomodulator. In addition, $\beta$-glucan could be used clinically for the treatment of diseases such as cancer therapy in the young.