• 약학회지
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• 제42권3호
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• pp.302-306
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• 1998

In the previous study we described the antitumor activity of GLB, a protein-polysaccharide fraction of the growing tips of Ganoderma lucidum, against sarcoma 180 solid tu mor in ICR mice. In this study we investigated the stimulatory activity of GLB on macrophages. When analyzed using a flow cytometer, GLB ($100{\mu}g/ml$) was found to increase the phagocytic activity of the BALB/c mouse peritoneal macrophages as well as chicken macrophage BM2CL cells against FITC-labeled C.albicans by 55.2% and 21.2%, respectively. GLB also increased the spreading and the expression of MHC class II molecules of BM2CL cells as well as the mouse peritoneal macrophages. From these results, it is clear that GLB is a strong stimulator to the macrophages.

• 생약학회지
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• 제41권2호
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• pp.108-114
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• 2010

The rhizome of Cibotium barometz has been used for variety of bone disease as a traditional medicine. In the present study, we examined the antioxidant and anti-inflammatory activities of 85% methanol extract of C. barometz. C. barometz exhibited potent scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide radical and nitric oxide radical. In IFN-$\gamma$/LPS-stimulated mouse peritoneal macrophage model, C. barometz suppressed nitric oxide production and IL-6 secretion dose-dependently. Moreover, C. barometz showed decreased iNOS and COX-2 expression without notable cytotoxicity. These results suggest that C. barometz may be an useful agent as an antioxidant and anti-inflammatory agent.

• 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.

• 생명과학회지
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• 제27권8호
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• pp.873-878
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• 2017

본 연구는 대식세포 활성화 과정에서 NQO1의 역할을 확인하는 것이다. 대식세포의 활성화 정도는 배양액으로 분비하는 IL-6와 $TNF-{\alpha}$ 양을 측정하여 평가하였다. 먼저 NQO1 WT 생쥐와 NQO1 KO 생쥐에서 각각 분리한 복강대식세포의 활성화 정도를 비교해 보았다. 특이하게도 NQO1 KO 복강대식세포가 NQO1 WT에 비해서 더 높게 활성화되어 있었다. 또한 일반 생쥐의 복강대식세포에 NQO1 억제제(dicumarol)을 처치한 경우에도 강한 활성이 유도됨을 확인하였다. Dicumarol을 처치한 RAW264.7 (대식세포주)에 서도 강한 활성화가 관찰되었다. 이는 NQO1이 대식세포의 활성화 과정을 억제하는 경로와 연관되어 있음을 보여준다. 더욱이 dicumarol을 처치하여 NQO1의 기능을 억제시킨 다양한 대식세포에서 $I{\kappa}B$ 단백질이 유의하게 감소한다는 사실을 확인하였다. 대식세포 활성화 과정을 매개하는 주요 신호분자가 $NF{\kappa}B$이며 이 분자에 대한 억제자가 $I{\kappa}B$라는 사실들을 감안할 때, NQO1의 기능이 $I{\kappa}B$ 단백질변성 억제와 연관되어 있으며 이를 통해 대식세포의 활성화를 차단했을 가능성이 있다. 본 연구는 향 후 대식세포 활성화 과정을 조절하는 NQO1의 역할을 규명하는데 있어서 중요한 기초 결과가 될 것이다.

• 한국식품영양과학회지
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• 제29권2호
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• pp.342-348
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• 2000

In this experiment, we show the effects of herbal plant extracts on the production of nitric oxide (NO) and TNF-$\alpha$. The extracts of Angelica gigas, Astragalus membranaceus, Acanthopanax sessiliflorus and Houttuynia cordata had no effect on NO synthesis by itself in mouse macrophage cell line (RAW264.7). However, the stimulation with these extracts in the presence of murine interferon-${\gamma}$(mIFN-${\gamma}$) resulted in increased NO synthesis. When these extracts were used in combination with mIFN-${\gamma}$, there were a marked cooperative induction of NO and TNF-$\alpha$ synthesis in a dose-dependent manner. The same results were obtained in the mouse peritoneal macrophages used. The optimal concentration of these extracts on NO synthesis was shown at 100$\mu\textrm{g}$/mL with 100U/mL of mIFN-${\gamma}$. NO synthesis was inhibited by NG-monomethyl-L-arginine. When cell lines were treated with extracts, the expression of inducible NO synthetase (iNOS) was markedly increased in RT-PCR analysis. In addition, synergy between mIFN-${\gamma}$ and extracts was dependent on extracts-induced tumor necrosis factor-$\alpha$(TNF-$\alpha$). These results suggest that water extracts of herbal plants can induce iNOS, NO and TNF-$\alpha$ synthesis of mouse macrophage cell line (RAW264.7) and peritoneal macrophages in combination with mIFN-${\gamma}$.

• Parasites, Hosts and Diseases
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• 제32권3호
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• pp.185-194
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• 1994

T. gonnii의 Beverley주를 감염시킨 마우스(감염군)로부터 분리한 복강대식세포에 cytokine의 종류 및 농도에 따른 대식세포의 활성화 정도를 평가하기 위하여 복강대식세포 단세포층에 medium, 조제 Iymphokine, 재조합 tumornecrosis $factor-{\alpha}{\;}(TNF-{\alpha})$. 재조합 $interferon-{\gamma}{\;}(IFN-{\gamma})$, 및 재조합 $IFN-{\gamma}와{\;}TNF-{\alpha}$를 함께($IFN-{\gamma}/TNF-{\alpha}$) 처치한 후, 각 처치군별 $H_2O_2{\;}생산량,{\;}NO2^{-}$ 생산량 및 T. gondii의 대식세포내 침투억제능을 측정하였다. 감염군의 복강대식세포에 $IFN-{\gamma}{\;}처치시{\;}NO2^{-}$ 생산량은 농도에 따라 유의하게 증가하였으나 그외의 처치군에서는 농도에 따른 유의한 차이가 없었다. 감염군 대식세포에 $IFN-{\gamma}나{\;}IFN-{\gamma}/TNF-{\alpha}$ 처치시 $H_2O_2$ 생산량이 medium처치군보다 유의하게 증가하였으며. $NO2^{-}$ 생산량은 $TNF-{\alpha},{\;}IFN-{\gamma}나{\;}IFN-{\gamma}/TNF-{\alpha}$ 처치시 유의하게 증가하였다. 감염군에 cytokine 처치시 T. gondii의 대식세포내 침투억제능은 medium 처치시보다 모두 증가되었다 또한 정상군과 감염군의 $H_2O_2$ 생산량, $NO2^{-}$ 생산량 및 T. gondii의 대식세포내 침투억제능을 상호 비교시 $IFN-{\gamma}$ 처치군은 유의한 차이를 나타냈으나 그 외의 cytokine 처치군에서는 유의한 차이를 나타내지 않았다. 이상의 성적으로 보아 $IFN-{\gamma}$가 Toxoplosma감염 마우스 복강대식세포의 활성화에도 중요한 역할을 함을 알 수 있었다.

• 생명과학회지
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• 제23권6호
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• pp.779-788
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• 2013

본 연구는 5주간의 고지방 식이(45% 지방)가 복강 대식세포의 면역 반응에 미치는 효과를 분석하였다. C57BL/6 마우스(4주령, N=16)를 2집단으로 나누어 고지방 식이집단(HD, N=8)은 45% 지방 함량 고지방식이를 정상 식이집단(ND, N=8)은 정상식이(10% 지방)를 5주간 실시하였다. 복강 대식세포는 복강세척법을 이용하여 획득하였으며, LPS (lipopolysaccharide, $1{\mu}g/ml$, 24시간)를 이용하여 배양하였다. 체중은 고지방식이 후 유의하게 증가하였으며, LPS 처치 후 HD그룹의 산화질소, IL-$1{\beta}$ 및 IFN-${\gamma}$ 생성량은 ND그룹에 비하여 유의하게 낮았다. 그러나 두 집단에서 TNF-${\alpha}$와 IL-12의 생성량은 유의한 변화가 없었다. 이러한 결과는 비만 시 대식세포의 식균작용, 산화질소, IL-$1{\beta}$ 및 IFN-${\gamma}$ 생성량이 낮아짐에 따라 면역반응과 항원자극 감수성이 저하되는 것으로 사료된다.

• 생약학회지
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• 제42권3호
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• pp.253-259
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• 2011

Macrophages play a vital role in the innate immune system involving defensive cytokines such as TNF (tumor necrosis factor)-${\alpha}$ and nitric oxide (NO). Therefore, we try to elucidate the anti-inflammatory activity of Chaga mushroom (Inonotus Obliquus, IO) in murine macrophages. Raw 264.7 cells and peritoneal macrophages of mice were cultured with or without LPS/LPS + IFN-${\gamma}$ in the presence of IO aqueous extracts (IOE 0.2, 2, 20, 100 ${\mu}g$/mL) for 24 hr and 48 hr, respectively. Exposure of IOE caused the decrease of NO production and increase of TNF-${\alpha}$ production in dose-dependent manner in activated peritoneal macrophage in vitro. To further investigate anti-inflammatory effects of IO ex vivo, we orally administrated capsaicin (PC, 3 mg/kg/day) and IOE (100, 200, 400 mg/kg/day) for 4 consecutive days to C57BL/6 mice (7~9 weeks old, female), then observed the NO secretion and cytokine (TNF-${\alpha}$) production of LPS/LPS + INF-${\gamma}$-stimulated peritoneal macrophages. IOE inhibits NO secretion in dose-dependent manner both ex vivo and in vitro and increases the production of TNF-${\alpha}$ in vitro. In addition, we found that IOE possessed suppressive effects of LPS-stimulated TNF-${\alpha}$, IL-$1{\beta}$, COX-2, as well as iNOS expressions in Raw 264.7 cells. These findings indicate that IOE suppress not only the LPS-induced NO overproduction of murine peritoneal macrophages, but also iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ overexpression of LPS-induced Raw 264.7 cells. Consequently, our results suggest that IO may have the anti-inflammatory effects via suppression of the inflammatory cytokines and mediators, and be useful for the treatment of inflammatory diseases.

• 한국식품영양학회지
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• 제21권2호
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• pp.204-209
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• 2008

The present study examined the ex vivo effect of Job's tear on immune function. Seven to eight week old mice(Balb/c) were fed a chow diet ad libitum two different concentrations (50 and 500 mg/kg BW) of water extract of Job's tear were orally administ every other day for two weeks. The results indicated that macrophage activation had occurred in the mice receiving 50 mg/kg B. W. of Job's tear water extract. Overall, using a mouse model, this study demonstrated that Job's tear extract may enhance immune function by regulating the $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ and IL-10 cytokine production capacity of activated macrophages in mice. This study may suggest that supplementation of Job's tear water extracts may enhance the immune function by regulating the enhancing the cytokine production by activated macrophage ex vivo.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.