• Journal of Animal Science and Technology
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• v.47 no.6
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• pp.947-954
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• 2005

This study was conducted to investigate the effects of hydrolyzed Lactobacillus supplementation with digestive enzymes treatment on the macrophage activation, the induction of nitric oxide(NO), interleukin (IL)-6 and tumor necrosis factor(TNF)-$\alpha$. The RAW 264.7 murine macrophage was exposed to porcine Lactobacillus strains which were digested with both pepsin and pancreatin. The production of NO, TNF-$\alpha$ and IL-6 in the macrophage were strain and dose-dependent, respectively. The induction of NO and cytokines were higher in both 3149 and 3146 strains compared with other Lactobacillus strains. Overall, the level of NO was observed at the lower range between 10 and 150 μg hydrolysates per ml, whereas IL-6 and TNF-$\alpha$ were observed at relatively higher concentration between 50 and 300 μg hydrolysates per ml. Lactobacillus strains which produced a high level of NO also showed a high induction of TNF-$\alpha$ and IL-6. Therefore, the present results suggest that hydrolysates of Lactobacillus strains are related to induction of several macrophage mediators, and then it could be beneficially used to modulate gastrointestinal immune function of the host. Also, the methodogly employed in this study might be useful to investigate the effects of lactic acid bacteria on gastrointestinal immunity.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.174-180
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• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• YAKHAK HOEJI
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• v.44 no.2
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• pp.182-188
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• 2000

High soy consumption leading to high exposures of soy isoflavones has been associated with a reduced risk of cancers at many sites. As part of a study focusing on the chemopreventive mechanisms, we have investigated the modulating effects of daidzein and genistein, a prominent and more bioavailable isoflavone in soy foods, on murine immune function. Daidzein (50 mg/kg) or genistein (50 mg/kg) was administered p.o. once a day for 7 days in BALB/c mice. Daidzein decreased the mitogen-stimulated proliferation of murine splenocyte, but genistein increased it. Daidzein stimulated the secretion of interleukin-4, but inhibited the secretion of ${\gamma}$-interferon, interleukin-2 and tumor necrosis factor-$\alpha$. Genistein stimulated the secretion of ${\gamma}$-interferon, interleukin-2 and tumor necrosis factor-$\alpha$, but inhibited the secretion of interleukin-4. Daidzein and geiustein inhibited the production of nitric oxide and enhanced the phagocytic activity in peritoneal macrophage. These results suggest that cancer preventive effects of daidzein is partly concerned with the secretion of $T_{H}$2 cells cytokine and the activation of macrophage phagocytosis, and genistein is partly concerned with the secretion of $T_{H}$l cells cytokine, tumor necrosis factor-$\alpha$ and the activation of macrophage phagocytosis.sis.

• Korean Journal of Veterinary Service
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• v.21 no.1
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• pp.41-56
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• 1998

These experiment was carried out to investigate the pulmonary lesions and the function of alveolar macrophages in rats exposed to cement dusts. 1. The number of total cells in bronchoalveolar lavage fluid(BAL) increased remarkably in 1st month. As time goes by, tend to less and less in numbers. 2. The number of neutrophil and lymphocytes obtaining from the total cell of BAL increased remarkably in first month, but as time goes by, they tended to grow less and less in number. Macrophages decreased gradually after being temporarily augmentation. 3. Histipathologically, the thickening of alveolar walls, alveolar interstitial, and infiltrated macrophages containing cement dusts.

• Korean Journal of Plant Resources
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• v.33 no.3
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• pp.183-193
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• 2020

Recently, as a natural substance has been emphasized interest in research to enhance the immune function. Green lettuce (Lactuca sativa L.) is a popular vegetable used fresh and it contains various phytochemicals and antioxidant compounds, and has been reported to have various physiological activities such as antibacterial, antioxidant, antitumor and anti-mutagenic. However, only a few studies have investigated on the mechanism of action of immune-enhancing activity of lettuce. Therefore, in this study, the immunomodulatory activities and potential mechanism of action of Green lettuce extracts (GLE) were evaluated in the murine macrophage cell line RAW264.7. GLE significantly increased NO levels by RAW264.7 cells, as well as expressions of immunomodulators such as iNOS, COX-2, IL-1β, IL-6, IL-12, TNF-α and MCP-1. Although GLE activated ERK1/2, p38, JNK and NF-κB, GLE-mediated expressions of immunomodulators was dependent on p38, JNK and NF-κB. In addition, TLR4 inhibition blocked GLE-mediated expressions of immunomodulators and activation of p38, JNK and NF-κB. Taken together, these results demonstrated that TLR4-MAPK/NF-κB signalling pathways participated in GLE-induced macrophage activation and GLE could be developed as a potential immunomodulating functional food.

• 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.

• 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.

• 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.

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.174.1-174
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• 2003

No Abstract, See Full Text

• Journal of Life Science
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• v.33 no.5
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• pp.397-405
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• 2023

Although glutathione (GSH) has been shown to play an important role in the prevention of oxidative damage as an antioxidant, studies on immune regulation by it have not been properly conducted. In this study, we investigated whether luthione^®, a reduced GSH, has an immune enhancing effect in murine macrophage RAW 264.7 cells. The results of flow cytometry and immunofluorescence experiments indicated that luthione increased phagocytic activity, a representative function of macrophages, compared to the control cells. According to the results of the cytokine array, the expression of interleukin (IL)-5, IL-1β, and IL-27 was significantly increased in the luthione-treated cells. Luthione also enhanced the production of tumor necrosis factor-α and IL-1β through increased expression of their proteins, and increased release of the immune mediators such as nitric oxide (NO) and prostaglandin E₂ was associated with increased expression of inducible NO synthase and cyclooxygenase-2. In addition, the expression of cluster of differentiation 86, an M1 macrophage marker, was dramatically enhanced in RAW 264.7 cells treated with luthione. Furthermore, as a result of heat map analysis, we found that cytokine signaling 1/3-mediated signal transducer and activator of transcription/Janus tyrosine kinase signaling pathway was involved in the immunomodulatory effect by luthione. In conclusion, our data suggested that luthione could act as a molecular regulator in M1 macrophage polarization and enhance immune capacity by promoting macrophage phagocytic function.