• Archives of Pharmacal Research
• /
• 제27권2호
• /
• pp.217-224
• /
• 2004

Previously, we reported that water-extracted Acanthopanax senticasus exhibited anti-meta-static activity by stimulating the immune system. In this study, we fractionated glycoproteins (EN-SP) from the soluble protein layer (GF-AS) of A. senticasus and determined their basic chemical properties. We also investigated the anti-tumor and immunostimulating activities of the fractionated glycoprotein, EN-SP. We found that intravenous (i.v.) administration of GF-AS dramatically inhibited metastasis of colon26-M3.1 carcinoma cells to the lung in a dose-dependent manner. In vitro analysis showed GF-AS to enhance the proliferation of splenocytes. GF-AS also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-1$\beta$, TNF-$\alpha$, IL-12 and IFN-${\gamma}$. Furthermore, the production of these cytokines was partially blocked when peritoneal macrophage was cultured with the polyclonal antibodies against GF-AS. The depletion of NK cells by rabbit anti-asialo GM1 serum partly abolished the inhibitory effect of GF-AS on lung metastasis of colon26-M3.1 cells. Using gel filtration, EN-SP, an active glycoprotein fraction, is isolated from GF-AS. While both GF-AS and EN-SP stimulated the proliferatation of splenocytes of normal mice, EN-SP showed higher anti-metastatic activity and more potently stimulated the proliferation of splenocytes compared to GF-AS. These results suggest the use of EN-SP, the fractionated glycoprotein from A. senticasus, can be used as a therapeutical reagent to prevent or inhibit tumor metastasis.

• 대한본초학회지
• /
• 제28권5호
• /
• pp.45-52
• /
• 2013

Objectives : This study aims at examining the immuno-modulating activity in the fermentative extract of the root of Scutellaria baicalensis Georgi (Scutellariae Radix) on the production of inflammatory mediator in LPS-stimulated RAW264.7 mouse macrophages. Method : Measurements were done for the influences on the cell viability, generation of hydrogen peroxide in cells and nitric oxide (NO) generation using the macrophage of mouse with the specimen SBS as the fermentative extract of Scutellariae Radix (SBS) with Saccharomyces cerevisiae STV89. Result : As a result of carrying out MTT assay to check the cellular toxicity of the fermentative extract of Scutellariae Radix, any excessive toxicity to the macrophage did not occur from treatments by concentration for SBS. SBS increased the generation of hydrogen peroxide in the macrophage. SBS suppressed the NO generated in macrophages and SBS concentration higher than $25{\mu}g/mL$ significantly suppressed the increased NO generated in LPS-stimulated macrophages. SBS concentration higher than $25{\mu}g/mL$ significantly suppressed the generation of IL-6, IL-10, IL-12p40 and MCP-1 in LPS-stimulated macrophages. Conclusion : Our findings indicate that SBS has an immuno-modulating activity in macrophage activation through suppressing the generation of inflammatory substances, NO, IL-6, IL-10, IL-12p40 and MCP-1.

• 대한본초학회지
• /
• 제28권5호
• /
• pp.113-119
• /
• 2013

Objectives : The purpose of this study was to investigate the effects of Angelicae Gigantis Radix Water Extract(AG) on the production of proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide(LPS). Method : RAW 264.7 cells were cotreated with AG(50 and 100 ug/mL) and lipopolysaccharide(LPS; 1 ug/mL) for 24 hours. After 24 hour treatment, using Bead-based multiplex cytokine assay, concentrations of various cytokines such as interleukin(IL)-6, IL-$1{\beta}$, IL-10, tumor necrosis factor-alpha(TNF-${\alpha}$), granulocyte colony-stimulating factor(G-CSF), granulocyte macrophage colony-stimulating factor(GM-CSF), interferon inducible protein-10(IP-10), leukemia inhibitory factor(LIF), lipopolysaccharide-induced chemokine(LIX), monocyte chemoattractant protein-1(MCP-1), macrophage colony-stimulating factor(M-CSF), macrophage inflammatory protein(MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-2, Regulated on Activation, Normal T cell Expressed and Secreted(RANTES) and vascular endothelial growth factor(VEGF) were measured. Result : AG significantly inhibited LPS-induced production of TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, and M-CSF from LPS-stimulated RAW 264.7 cells at the concentrations of 50 and 100 ug/mL. AG significantly inhibited LPS-induced production of MIP-$1{\beta}$, MIP-2, GM-CSF, and IL-6 from LPS-stimulated RAW 264.7 cells at the concentrations of 50 ug/mL. AG significantly inhibited LPS-induced production of VEGF from LPS-stimulated RAW 264.7 cells at the concentrations of 100 ug/mL. But AG did not show any significant effect on the production of MCP-1, LIF, LIX, IP-10 and IL-$1{\beta}$ from LPS-induced RAW 264.7 cells. Conclusion : These results suggest that AG has anti-inflammatory effect related with its inhibition of proinflammatory mediators such as TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, MIP-$1{\beta}$, MIP-2, GM-CSF, IL-6, VEGF and M-CSF in LPS-induced macrophages.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권3호
• /
• pp.257-265
• /
• 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.

• 한국식품과학회지
• /
• 제50권4호
• /
• pp.437-443
• /
• 2018

본 연구는 꿀벌 꽃가루 열수 추출물(BPW)의 면역 활성에 관하여 알아보기 위하여, 선천면역과 적응면역에서 중심 역할을 수행하는 큰포식세포에 BPW를 처리하여 세포 생존율, NO 분비능, 사이토카인($TNF-{\alpha}$, IL-6, $IL-1{\beta}$) 분비능과 메커니즘 분석을 통한 신호전달에 관하여 관찰하였다. BPW를 큰포식세포에 처리하여 면역활성에 관하여 알아봤을 때, 큰포식세포 면역활성의 대표적인 바이오마커인 NO, 사이토카인의 분비능과 iNOS의 세포내 발현이 BPW 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 또한 활성화된 탐식 세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식세포의 항원제시에 밀접한 관련이 있는 주조직적합성 복합체(MHC class I과 II)의 발현이 BPW 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 기전분석 결과, BPW의 처리는 MAPKs의 인산화와 $NF-{\kappa}B$의 핵 내 이동성을 증가시켜 면역활성을 증가시키는 것으로 관찰되었다. 따라서 BPW의 처리는 큰포식세포의 활성을 유도시켜 면역활성을 조절하는 것으로 관찰되었다.

• 한국미생물·생명공학회지
• /
• 제35권2호
• /
• pp.118-127
• /
• 2007

본 연구는 마우스를 대상으로 유기게르마늄 강화효모 경구투여에 의한 면역조절작용 효과를 확인하고자 하였다. 마우스를 대상으로 9일간 경구투여한 결과 대조군인 게르마늄 비강화 효모 투여군에 비해 복강대식세포, B세포, NK 세포의 활성이 현저히 증가한 것으로 확인되었으며, 최종 실험결과 대식세포는 게르마늄 강화효모 투여 후 식세포활성, 주화성, 부착성, rosette 형성능 현저히 증가하였다. Superoxide $anion(O_2^-)$ 생성능은 대조군에 비해 유기게르마늄 강화군 투여군에서 3배 활성이 증가하였으며, NO 생성능과 $TNF-{\alpha}$ 생성능도 농도의존적으로 증가하였다. B-세포 활성화에 의한 cytolytic activity 증가에 의한 PFC형성능도 게르마늄 비강화 효모에 비해 현저히 증가하였으며 상업화 유기게르마늄으로 알려지고 있는 Ge-132에 비해 2배 이상 높은 활성이 확인되었다. Cytotoxic acivity에 의한 항 종양활성에서는 양성대조군인 Doxorubicin 투여군에서와 유사한 저해활성을 나타내었으며 고용량 유기게르마늄 효모(2,400 mg/kg) 투여시 60%의 종양활성 억제효과가 확인되었다. 이러한 결과를 종합해 볼 때 유기게르마늄 강화효모가 실험동물 뿐만 아니라 인체의 유용한 면역조절제로서의 이용성이 기대된다.

• 대한임상검사과학회지
• /
• 제53권2호
• /
• pp.158-164
• /
• 2021

고중성지방혈증은 죽상동맥경화증의 주요한 위험 요인 중 하나이다. 중성지방은 대식세포의 세포 사멸을 유도하여 죽상동맥경화증 발생에 기여하는 것으로 알려져 있다. 본 연구팀은 앞선 연구에서 대식세포의 중성지방-유도 세포 사멸이 pannexin-1 활성화에 의한 세포 외 ATP 농도 증가, caspase-2와 caspase-1 활성화, caspase-8을 포함한 apoptotic caspase 활성화 경로로 일어나는 것을 보고하였다. 한편 다른 연구들에서는 세포 내 다른 여러 기전에서 caspase-8이 caspase-1과 -2의 상위 단백질이라 보고하고 있다. 따라서 본 연구에서는 caspase-8이 중성지방-유도 대식세포 사멸 과정에서 상위단백지로 영향을 미치는지 여부를 조사하기 위해 수행되었다. 본 연구진은 caspase-8이 중성지방-유도 대식세포 사멸 과정에서 caspase-3 활성화 및 PARP 절단을 유도하였다. 다음으로 중성지방이 처리된 대식세포에서 caspase-8 억제 시, caspase-8의 상위 단백질로 보고한 caspase-1 및 -2의 활성이 감소하는 것을 확인하였다. 또한 ATP 처리 시 caspase-8 억제제 처리에 의해 감소된 caspase-2의 활성이 회복되는 것을 확인하였다. 위의 결과를 통해 caspase-8이 중성지방-유도 대식세포 사멸 과정에서 세포 외부 ATP 농도 증가에 관여하는 단백질 또는 그 상위 기전에 양성피드백 방식으로 영향을 미쳐 caspase-1과 -2를 활성화하여 중성지방-유도 대식세포 사멸을 증진시킴을 알 수 있다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.179-180
• /
• 2002

The phospholipase $A_2$($PLA_2$) family represents a diverse group of enzymes that hydrolyze sn-2 fatty acid from the cell membrane. Several mammalian cytosolic $PLA_2$ and secretory $PLA_2$(s$PLA_2$) have been characterized and classified into different families. At present, 12 distinct sPLA$_2$s have been identified in mammals and classified into different groups, depending on their primary structures as characterized by the number and position of cysteine residues. (omitted)

• 한국작물학회:학술대회논문집
• /
• 한국작물학회 2006년도 한국약용작물학회 공동춘계학술발표회
• /
• pp.652-653
• /
• 2006

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.151.1-151.1
• /
• 2002