• Biomolecules & Therapeutics
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• 제8권3호
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• pp.217-222
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• 2000

Bacterial components and their derivatives have been reported to mediate various immunomodulating activities and to activate immune cells including macrophage. In this study, the secretory and cellular macrophage response to teichoicated fragments (TFs) from pneumococcal cell wall subcomponent were examined. Tumoricidal activity was measured by MTT assay and secretory molecules were assessed by biological assay. After stimulation of macrophages with various doses of TFs for 18hrs, secretion of TNF-$\alpha$, nitrite and $H_2O$$_2$ were significantly increased as compared to medium-treated control. In addition, tumorcidal activity of TFs-treated macrophages was enhanced, whereas production of IL-1 and IL-6, and phagocytic activity were not induced. These data suggest that TFs is a potent inducer of macrophage secretory and cellular activities.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.457-462
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• 2002

Oregonin, a diarylheptanoid derivative from Alnus hirsuta Turcz, Betulaceae, was evaluated for its antitumor activity. Oregonin, known to have an antitumor function, and is a novel immunomodulator, which may augment macrophage activity. MTT assays and NO production tests were performed in order to investigate the cytotoxicity of oregonin in tumor cells and to examine its influence on macrophage in detail. In this study, the tumoricidal activity was also evaluated by a MTT assay. The cytotoxicity measurements in the oregon in-treated group both in vitro and in vivo showed a significant difference from that of the control group. In vivo, oregonin significantly increased NO production in a dose-dependent manner, and in vitro, the thioglycolate-induced inflammatory macrophages increased NO production in a dose-dependent manner after incubation. These results suggest that oregonin reacts with both the inflammatory and non-inflammatory macrophages in a similar way.

• 대한방사성의약품학회지
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• 제7권1호
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• pp.41-49
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• 2021

Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in anti-inflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

• BMB Reports
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• 제53권11호
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• Journal of Ginseng Research
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• 제40권2호
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• pp.196-202
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• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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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.

• 동의생리병리학회지
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• 제24권4호
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• pp.586-591
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• 2010

Chemokine and Growth Factor are major mediumtors of immuno-inflammatory pathway. The purpose of this study is to investigate whether productions of Chemokine and Growth Factor in lipopolysaccharide (LPS)-induced mouse macrophage RAW 264.7 cells are modulated by Gallic acid (GA), which is easily founded in tannin-containing natural materials such as red wine, green tea, grape juice, and Corni Fructus. Productions of Chemokine and Growth Factor were analyzed by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. At first, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, the antibody-conjugated beads were added and incubated for 30 minutes. After incubation, detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System. Based on fluorescence intensity, concentrations of Chemokine and Growth Factor were determined. The results of the experiment are as follows. GA significantly inhibited the production of interferon-inducible protein (IP)-10, keratinocyte-derived chemokine(KC), and vascular endothelial growth factor (VEGF) in LPS-induced RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). GA significantly inhibited the production of monocyte chemoattractant protein-1(MCP-1) and macrophage-colony stimulating factor(M-CSF) in LPS-induced RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). GA diminished the production of granulocyte macrophage-colony stimulating factor (GM-CSF) in LPS-induced RAW 264.7 cells. But GA did not show the inhibitory effect on the production of leukemia inhibitory factor (LIP) and macrophage inflammatory protein (MIP)-2 in LPS-induced RAW 264.7 cells. These results suggest that GA has the immuno-modulating activity related with its inhibitory effects on the production of IP-10, KC, MCP-1, VEGF, and M-CSF in LPS-induced macrophages.

• 한국식품영양과학회지
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• 제44권7호
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• pp.1079-1083
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• 2015

본 연구는 양조과정의 부산물인 주박으로부터 분리한 다당류(JPS)가 초기 면역반응에 중추적인 역할을 수행하는 대식세포에서 활성화를 유도하는지에 관한 여부를 알아보기 위해서 수행되었다. 주박에서 분리한 다당류를 마우스 유래 대식세포인 RAW264.7 cell에 처리하였을 때 대식세포의 활성화의 지표인 NO와 cytokine(IL-6, TNF-${\alpha}$)의 분비가 증가되었다. 또한 이러한 NO와 cytokine의 증가의 원인에 관한 면역기전에 관하여 알아본 결과 JPS의 처리는 MAPKs(ERK, JNK, p-38)의 인산화를 촉진시켜 NF-${\kappa}B$의 활성을 유도하여 면역세포의 활성인자들의 분비를 촉진시킨 것으로 관찰되었다.

• KSBB Journal
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• 제5권2호
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• pp.113-118
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• 1990

생체내 중요한 면역조절물질의 하나인 IL-l은 주로 Macrophage로부터 분비되어 각종 면역반응에 관여하는 것으로 알려져 있는데 이러한 Macrophage에 의한 IL-I 생성에 미치는 Histamine의 효과를 검토하고자 Mac-rophage-like cell line인 $P388D^1$세포에 의한 IL-1생성에 미치는 Histamine의 첨가효과는 $10^-^8M~10^-^3M$에 이르기까지 전 범위에서 농도의존적으로 IL,-1생성을 촉진시켰으며 첨가후 배양시간에 있어서는 24~36시간이 가장 크게 상승되었다. Histamine에 의한 Macropahge로 부터의 IL-1생성은 EGTA 및 $Co^2^+$의 첨가로 인하여 농도의존적으로 저하되었으며 이 결과는 Histamine의 IL-1 생성촉진작용이 세포내로의 $Ca^2^+uptake가 signal 역할을 하고 있음을 시사한다. $P388D_1$세포로의 $Ca^2^+$uptake양을 동정한 결과는 Histamine의 $10^-^7M$에서 $10^-^3M$까지 농도의존적으로 $Ca^2^+3M$유입이 촉진되는 결과를 나타내었다.

• Journal of Ginseng Research
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• 제43권3호
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• pp.394-401
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• 2019

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.