• 한국영양학회:학술대회논문집
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• 한국영양학회 2003년도 연합학술대회
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• pp.284.2-284.2
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• 2003

• Clinical and Experimental Reproductive Medicine
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• 제48권2호
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• pp.124-131
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• 2021

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

• 약학회지
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• 제54권2호
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• pp.134-141
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• 2010

It is well known that the numbers and functions of immune-associated cells are increased by saponins and polysaccharides in ginseng. In this study, the mixture of polysaccharide and saponin (MPS) from Panax ginseng is applied to LPS- activated RAW 264.7 cells. The production of NO and the gene expression of IL-6 and TNF-$\alpha$ are decreased in LPSactivated RAW 264.7 cells and the expression of arginase II and PD-1L genes is decreased in LPS-untreated macrophages. Therefore, the mixture of saponin and polysaccharide from Panax ginseng could be used in order to regulate immune responses.

• Parasites, Hosts and Diseases
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• 제35권3호
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• pp.189-196
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• 1997

활성화된 대식세포에서 생산되는 NO가 질편모충에 대해 세포독성이 있는지를 관찰하고자 질소 중간산물에 영향을 주는 약제를 첨가한 후 nitrite 생산 및 세포독성에 미치는 영향을 관찰하였다. 대식세포로는 마우스(BAkBlc) 복강 대식세포와 마우스 복강 내 종양세포인 RAW264.7 세포로 LPS(lipopolysaccharide)나 $rIFN-{\gamma}$로 활성화시켜 사용하였다. 세포독성의 측정을 위해서 질편모충을 methyl-[$^3H$]-thymidine으로 표지하였고 NO의 측정은 Griess reagent를 사용하여 시행하였다. 마우스 복강 대식세포는 LPS로 활성화시켰을 때 질편모충에 대한 세포독성이 대조군에 비해 증가하였고, RAW264.7 세포는 $rIFN-{\gamma}$ 또는 $rIFN-{\gamma}$ 및 LPS로 활성화시켰을 때 대조군에 비해 세포독성 및 nitrite 생산량은 유의하게 증가하였다. LPS로 활성화시킨 마우스 복강 대식세포와 $rIFN-{\gamma}$로 활성화시킨 RAW264.7 세포에 NO 생산에 영향을 주는 NG-monomethyl-L-arginine(L-NMMA), NC-nitro-L-arginine methyl ester(NAME), arginase를 첨가하였을 때 약제 농도를 증가시킴에 따라 질편모충에 대한 세포독성과 nitrite 생산이 감소하였다. NO synthase coractor인 tetrahydrobiopterin($H_4B$)을 마우스 복강 대식세포에 넣었을 때 질편모충 에 대한 세포독성이 증가하였다. Ferrous sulfate를 두 종류의 활성화시킨 대식세포에 첨가하였을 때 질편모충에 대한 세포독성과 nitrite생산이 감소하였다. 이상의 성적을 종합하면 대식세포의 활성화에 따라 NO 생산 및 세포독성이 증가하였고. NO 생산을 저하시키는 약제들은 활성화된 복강 대식세포 및 RAW264.7 세포에 의한 질편모충에 대한 세포독성을 현저히 감소시키는 것으로 보아 NO는 질편모충에 대한 대식세포의 숙주 방어기전에서 중요한 역할을 감당할 것으로 생각된다.

• Molecules and Cells
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• 제37권1호
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• Journal of Genetic Medicine
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• 제1권1호
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• pp.5-10
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• 1997

The amino acids formed by degradation of proteins ingested produce ammonia. The ammonia which is broken down and excreted as urea through a process known as the Klebs-Hensleit cycle or the urea cycle (Rezvani, 1995). The urea cycle consists of five enzymes necessary for the synthesis of carbamyl phosphate, citrulline, argininosuccinate, arginine, and urea: carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), and arginase (ARG) (Lloyd, 1992). Congenital deficiencies of the enzymes involved in the urea cycle are diseases that are almost fatal without treatment, showing symptoms like vomiting, lethargy, dyspnea, and coma due to hyperammonemia coming from the accumulation of ammonia and metabolic precursors resulting from the deficiency of one of these enzymes (Batshaw and Brusilow, 1983). Among these, the disease manifested by the congenital deficiency of argininosuccinate synthetase (AS) which is associated with the formation of argininosuccinate in citrulline is called argininosuccinate synthetase deficiency or citrullinemia. There have been two reports on this so far in Korea; one in July 1987 by Kim et al. and the other by Park et al. in 1995. We are to report a case of successful treatment of a child with citrullinemia who was transferred to our hospital due to dyspnea, lethargy, feeding difficulties, convulsions and cyanosis together with some document studies related to this case.

• 대한약침학회지
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• 제22권4호
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• pp.253-259
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• 2019

Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

• 대한한의학회지
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• 제21권3호
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• pp.20-30
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• 2000

Objective : This experiment was performed in order to study the effect of an aqueous extract of Salviae radix root(SRRAE) on NO production and NOS gene induction from macrophages Methods : To investigate dose-dependent effects of SRRAE for NO release on the $rIFN-{\gamma}-treated$ macrophages, the cells were incubated for 6 hrs in a medium containing $rIFN-{\gamma}$ (5 U/ml), stimulated with SRRAE and incubated in a CO2 incubator. The cells were treated with 5 U/ml $rIFN-{\gamma}$ plus 100 g/ml of SRRAE, Then, the cells were incubated with various concentrations of NGMMA at $37^{\circ}C$ for 48 hrs, Results : SRRAE had no effect on NO production by itself, whereas recombinant $interferon-{\gamma}(rIFN-{\gamma})$ alone showed modest activity, When SRRAE was used in combination with $rIFN-{\gamma}$, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SRRAE on NO production was shown at 6hrs after treatment with $rIFN-{\gamma}$. The SRRAE-induced production of NO was inhibited by NG-monomethyl- L-arginine(NGMMA) and arginase. $rIFN-{\gamma}$ in combination with SRRAE showed a marked increase of the expression of the inducible NOS(iNOS) gene. In addition, the effect of SRRAE was mainly dependent on the SRRAE-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. Conclusions : SRRAE induces NO production from macrophages as a result of SRRAE-induced $TNF-{\alpha}$ secretion. SRRAE may provide a second signal for synergistic induction of NO production in macrophages already induced to express iNOS gene by $rIFN-{\gamma}$.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3917-3922
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• 2015

Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exert immunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue of curcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcumin has received little attention so far. We have previously shown the potential biocompatibility, biodegradability and anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophages in the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end of intervention, the tumor volume and weight were significantly reduced in DNC groups compared to control (P<0.05). Histopathological data showed the presence of macrophages in tumor and spleen tissues. Real-time PCR results showed that DNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment with DNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage. The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastatic breast cancer in mice.

• Journal of Ginseng Research
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• 제42권1호
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• pp.68-74
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• 2018

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.