• 한방재활의학과학회지
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• 제23권2호
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• pp.1-15
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• 2013

Objectives : In present study, we investigated the effects of ginsenoside Rg3 on early-stage inflammatory response in spinal cord compression of rodents. Methods : Spinal cord injury(SCI) was induced by a vascular clip method(30 g, 5 min) on the spinal cord of mice. Rg3 was treated orally at 1 hour prior to the SCI induction. Messenger ribonucleic acid(mRNA) expression of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and cyclooxygenase-2(COX-2) was measured by the real-time polymerase chain reaction(RT-PCR). Microglia in the spinal cord tissue, neurophils and COX-2 in the peri-lesion and inducible nitric oxide synthase(iNOS) expression in the ventral horn of SCI induced rats were measured by immunohistochemical stain. Results : 1. Rg3 significantly reduced the mRNA expression of TNF-${\alpha}$, IL-1${\beta}$, and COX-2 in the spinal cord tissue compared with SCI group(p<0.05, p<0.01). 2. Rg3 significantly reduced the total number of activated microglia and proportion of phagocytic form in the total activated microglia compared with SCI group(p<0.05, p<0.01). 3. Rg3 significantly reduced myeloperoxidase(MPO) positive neurophil in the peri-lesion compared with SCI group(p<0.05). 4. Rg3 reduced the COX-2 expression in the tissue and motor neurons compared with SCI group. 5. Rg3 significantly reduced iNOS positive motor neurons in the ventral horn compared with SCI group(p<0.01). Conclusions : In conclusion, we demonstrated at first that treatment of ginsenoside Rg3 could reduce significantly the levels of inflammatory mediators in a spinal cord compression model of rodents. Therefore, these results suggested that ginsenoside Rg3 may be a useful antimiflamatory therapeutic candidate for SCI.

• Clinical and Experimental Pediatrics
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• 제52권2호
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• pp.234-241
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• 2009

목 적 : 가와사끼병에서 갑상샘 호르몬과 혈청 TNF-${\alpha}$, IL-6 및 NT-proBNP 농도와의 연관성을 알아보고자 하였다. 방 법 : 환자군으로 가와사끼병 환아 52명과 대조군으로 다른 열성 질환 환아 10명을 대상으로 하였다. 환자군의 치료 전 급성기와 치료 3-9일 후의 아급성기 때의 혈청과 대조군의 급성 발열기 혈청에서 갑상샘 호르몬과 TNF-${\alpha}$, IL-6, NT-proBNP를 각각 측정하여 비교하였다. 환자군에서는 심장 초음파검사로 관상동맥 병변의 유무를 조사하였다. 결 과 : 가와사끼병의 63.5%에서 저 $T_3$ 증후군($T_3$<100 ng/dL)이 동반되었다. 급성 가와사끼병의 $T_3$는 대조군에 비해 유의하게 낮았다($86.8{\pm}36.6$ vs $116.7{\pm}24.4$ ng/dL, P<0.05). 가와사끼병 환자군에서 $T_3$는 급성기에 감소하고 갑상샘 호르몬의 치료없이 아급성기에 증가하였으나($84.3{\pm}33.0$ vs $109.3{\pm}37.5$ ng/dL, P<0.01), 반대로 TNF-${\alpha}$, IL-6 및 NT-proBNP는 모두 급성기에 증가하고 아급성기에 감소하였다. 가와사끼병 환자군에서 저 $T_3$군(n=33)은 정상 $T_3$군(n=19)에 비해 신장 및 간기능의 차이는 없었고, NT-proBNP는 높았으며, IL-6는 약간 높은 경향을 보였다. 또한 $T_3$는 IL-6 (r=-0.12, P>0.05) 및 NT-proBNP(r=-0.54, P<0.001)와 반비례 관계를 보였다. 관상동맥 병변을 보인 가와사끼병 환아 4명 중 3명에서 $T_3$가 25.0-42.7 ng/dL로 매우 감소하였다. 면역글로불린 치료반응군(n=45)에 비해 저항군(n=7)에서 $T_3$는 더 낮았고($93.8{\pm}33.5$ vs $41.6{\pm}19.8$ ng/dL, P<0.001), IL-6와 NT-proBNP는 더 높았다. 결 론 : $T_3$는 가와사끼병의 급성기에 감소되며 아급성기에 갑상샘 호르몬의 치료 없이 정상화된다. $T_3$ 감소는 부분적으로 TNF-${\alpha}$ 보다는 IL-6의 작용에 의해 유발되며 NT-proBNP의 상승과 연관된다. 가와사끼병에서 $T_3$ 측정은 다른 열성 질환과의 감별진단에, 질병경과를 모니터하는데, 심근 손상의 초기 표식자로, 질병의 심한 정도를 예측하는데 이용할 수 있으리라 생각된다.

• Journal of Animal Science and Technology
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• 제53권3호
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• pp.203-209
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• 2011

Lysophosphatidic acid (LPA) is a small lipid molecule that plays an important role through LPA receptors (LPARs) in reproductive processes. Our previous study has shown maximal expression of LPAR3 in the uterine endometrium on day (D) 12 of pregnancy in pigs, the period when conceptus secretes various molecules such as estrogen and interleukin-$1{\beta}$ (IL1B) and initiates implantation. We determined that endometrial expression of LPAR3 was increased by conceptus estrogen in the previous study, but the effect of IL1B on LPAR3 expression has not been determined. Thus, in this study we examined whether LPAR3 expression was also affected by IL1B. Endometrial explant cultures from D12 of the estrous cycle showed that levels of endometrial LPAR3 expression did not changed in response to IL1B. We also investigated LPAR3 expression in the uterine endometrium on D12 and D30 of pregnancy from gilts with conceptuses derived from somatic cell nuclear transfer (SCNT). The expression of LPAR3 mRNA was lower in endometria from gilts with conceptuses resulting from SCNT compared with those from gilts with embryos resulting from natural mating on D12 of pregnancy, but it was not different between them on D30 of pregnancy. Our results indicate that estrogen of conceptus origin is responsible for induction of LPAR3 expression during the peri-implantation period and appropriate LPA signaling is impaired in the uterine endometrium with SCNT-derived conceptuses during the implantation period in pigs.

• 약학회지
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• 제52권5호
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• pp.402-406
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• 2008

Previously, we have shown that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has an anti-inflammatory activity in a rat paw-edema model. In the present study, we investigated an inhibitory effect of FPP-3 on the tumor necrosis factor (TNF)-${\apha}$-induced inflammatory cytokine response in HT-29 human colon epithelial cells. Treatment with FPP-3 significantly prevented the TNF-${\apha}$-induced attachment of leukocytes to HT-29 colon epithelial cells, which is one of the pathologic hallmarks in colon inflammation. The effect of FPP-3 was markedly superior than that of 5-aminosalicylic acid (5-ASA), a commonly used drug for the treatment of inflammatory bowel disease (IBD). The pretreatment with FPP-3 inhibited TNF-${\apha}$- induced monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 mRNA expressions. In addition, FPP-3 significantly suppressed TNF-${\apha}$-induced nuclear factor (NF)-${\kappa}B$ transcription activity. These results demonstrate that FPP-3 modulates intestinal inflammation via suppressing the NF-${\kappa}B$ dependent expressions of MCP-1 and IL-8, and suggest that FPP-3 may be a valuable agent for the treatment of IBD.

• Journal of Periodontal and Implant Science
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• 제29권4호
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• pp.979-995
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• 1999

본 연구에서는 치주질환과 관련이 깊은 것으로 알려진 구강내 spirochetes 균중 Treponema denticola 분쇄액(TDC)과 가장 최근에 분리 배양된 Treponema lecithinolyticum 분쇄액(TLC)이 치은섬유아세포의 cytokine 분비 및 matrix metalloproteinase(MMP) 활성에 미치는 영향을 알아 보기 위하여 균의 분쇄액을 치은섬유아세포에 처리한 후 Interleukin-6(IL-6)와 $Interleukin-1{\beta}(IL-1{\beta})$의 분비 증가 여부를 ELISA를 통하여 측정하였으며, 또한 gelatinase zymography와 gelatin 분해능 측정을 통하여 교원질 분해 효소의 하나인 pro-MMP-2(progelatinase A)의 활성화 여부를 측정한 결과 다음과 같은 결론을 얻었다. 1. TDC와 TLC가 치은섬유아세포의 IL-6 분비에 미치는 영향을 살펴 본 결과, TDC 와 TLC 처치군에서 세균 분쇄액이 없는 비처치군에 비해 IL-6 분비량이 증가하였으며 유의성 있는 차이가 있었다(p<0.05). 2. TDC 와 TLC로 처리한 치은섬유아세포의 $IL-1{\beta}$ 분비는 측정 가능치(1pg/ml)이하의 분비량이 관찰되었다. 그러므로 $IL-1{\beta}$의 분비에는 영향이 없는 것으로 보인다. 3. 치은섬유아세포에서 분비되는 분자량 72 kDa의 pro-MMP-2가 TDC와 TLC에 의해 활성형으로 발현되어 zymography상에서 62kDa의 위치에 clear band로 나타났다. 4. 치은섬유아세포가 분비하는 MMP-2의 gelatin 분해능이, TDC와 TLC 처치군에서 비처치군보다 높게 나타났으며 유의 성 있는 차이가 있었다(p<0.05). 5. TDC 처치군에서는 gelatin 분해능에 있어서 세균 자체의 serin protease의 영향이 있었으나 TLC 처치군에서는 치은섬 유아세포의 MMP에 의해서만 gelatin이 분해되었다. 이상의 결과를 보아 TDC와 TLC는 치은섬유 아세포를 자극하여 IL-6 의 분비는 증가시킬 수 있으나 $IL-1{\beta}$의 분비에는 영향을 미칠 수 없으며, 치은섬유아세포에서 분비되는 pro-MMP-2를 활성형으로 발현시켜 결합조직의 파괴를 야기함으로서 치주 질환의 병인론에 기여할 수 있음을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Journal of Ginseng Research
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• 제46권6호
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• pp.771-779
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• 2022

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA₁₆₀₀-PEG₁₀₀₀-PLGA₁₆₀₀ were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 ㎛ pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

• Restorative Dentistry and Endodontics
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• 제31권3호
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• pp.153-160
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• 2006

본 연구는 치수조직, 치은, 치주인대로부터 배양된 조직을 SP (Substance P)로 4시간 SP, CGRP (Calcitonin Gene-related Peptide) , Tumor necrosis factor-$\alpha$ (TNF-$\alpha$)로 8시간 자극 후 RNase Protection Assay를 시행하고, IL-8의 분비량을 측정해 다음 결과를 얻었다. 1. IL-8 mRNA는 모든세포에서 발현됐다. 2. IL-8 mRNA 발현은 SP ($10^{-5}M$)와 SP ($10^{-8}M$)로 4시간 자극 시 증가되지 않았다. 3. IL-8 mRNA 발현은 SP ($10^{-4}M$)와 CGRP ($10^{-6}M$)로 8시간 자극 시 증가되지 않았다. 4. TNF-$\alpha$ (2 ng/ml) 자극 시, IL-8 mRNA 발현이 증가됐다. 5. 치은 세포를 CGRP ($10^{-6}M$)로 8시간 자극 시, IL-8 분비량이 증가했다 (p<0.05). 6. 치주인대 세포를 SP ($10^{-4}M$)로 8시간 자극 시 IL-8 분비량이 증가했다 (p<0.05).

• 약학회지
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• 제52권1호
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• pp.62-66
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• 2008

In this study, we examined the inhibitory effects of propenone derivatives, 1,3-diphenyl-propenone (DPhP), 3-phenyl-1-thiophen-2-yl-propenone (PhT2P), 3-phenyl-1-thiophen-3-yl-propenone (PhT3P) and 1-furan-2-yl-3-phenyl-propenone (FPhP), on $TNF-{\alpha}$-induced nuclear factor (NF)-${\kappa}B$ activity and interleukin (IL)-8-induced monocyte adhesion to colon epithelial cells. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) that is previously reported as a $NF-{\kappa}B$ inhibitor suppressed $TNF-{\alpha}$-induced monocyte-epithelial cell adhesion in a concentration-dependent manner. The propenone derivatives, DPhP, PhT2P, PhT3P, FPhP, also inhibited $TNF-{\alpha}$-induced $NF-{\kappa}B$ activation in a similar degree to FPP-3. In a DPPH radical scavenging assay, none of the compounds showed DPPH radical scavenging activity, indicating that the inhibitory actions of the propenone derivatives on redox-sensitive $NF-{\kappa}B$ activity is not due to a simple free radical scavenging activity. In addition, the propenone derivatives also suppressed the IL-8-induced monocyte adhesion to colon epithelial cells. Furthermore, the effective concentrations of the propenone derivatives on both $NF-{\kappa}B$ activation as well as IL-8 induced monocyte-epithelial cell adhesion were 1000 times lower than 5-aminosalicylic acid (5-ASA), a clinically used drug for inflammatory bowel disease. These results suggest that the propenone derivatives may be a potential lead having a strong inhibitory activity against inflammatory cytokine-induced epithelial inflammation.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.163-170
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• 2016

We examined whether apigenin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the knee joint of rat to evaluate the potential chondroprotective effects of apigenin. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription - polymerase chain reaction (RT-PCR) was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and ADAMTS-5. In rabbit articular chondrocytes, the effects of apigenin on IL-$1{\beta}$-induced secretion and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of apigenin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, apigenin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Furthermore, apigenin inhibited the secretion and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that apigenin can regulate the gene expression, secretion, and activity of MMP-3, by directly acting on articular chondrocytes.