• 대한한의학회지
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• 제29권5호
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• pp.111-117
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• 2008

Objectives and methods : Previous mechanistic studies suggest the cyclooxygenase-2 (COX-2) inhibitors represent the good candidates against tumor progression. MeOH extract of the stem barks of Euonymus alatus induced the strong inhibition of COX-2. A phenolic compound responsible for the anti- COX-2 known to involve in tumor adhesion and invasion has been studied through the methanol extracts. The compound, rosmarinic acid (ROS-A) was an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. ROS-A showed a strong inhibitory effect of COX-2 activity in a concentration-dependent manner. Then we have measured the IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production related the immune regulation, induction of inflammatory related genes. Results and Conclusions :Hep3B cells produce proinflammatory cytokines of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ while ROS A inhibited the cytokines production. Since IL-1${\beta}$, IL-6 and TNF-${\alpha}$ need the transcription factors such as nuclear factor- ${\kappa}$B (NF-${\kappa}$B) and activated protein-1 (AP-1), we measured the transcription factors. ROS-A inhibited the activation of p65, p50, c-Rel subunits of NF-${\kappa}$B and AP-1 transcription factors. These findings indicate that ROS A from the stem bark of E. alatus inhibits proliferation in metastatic cancer cells. It was suggested that stem barks of E. alatus could be suitable for anti-cancer drugs.

• 혜화의학회지
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• 제9권2호
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• pp.315-324
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• 2001

To investigate the capacity of anti-inflammatory cytokines and biological response modifiers (BRMs) to induce IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene overexpression from mouse macrophages, we isolated the resident peritoneal macrophages from BALB/c mouse (8 week old) and incubated for 6 h with lipopolysaccaride (LPS) and Moschus moschiferus (MOMS) extracts. Analysis of inflammatory cytokines gene expression was carried out by RT-PCR amplification. Amplified PCR products were electrophoresed on 1.2% agarose gel, and the analysis (Ht) was used to 1D-density program. 1. LPS and MOMS extract treatments resulted in a significant decrease in IL-$1{\beta}$, IL-6, TNF-${\alpha}$ mRNA expression level compared with the LPS treatment. 2. Among four sample of MOMS, Inhibitory effects of MOMS-A and MOMS-D for inflammatory cytokines gene expression were to be fine compared with the MOMS-Band MOMS-C. According to the above data, Because the anti- tumoral and anti-inflammatory response activities of macrophage are known to be dependent on the production of inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) by macrophages, we suggest that evaluations of BRM for the reduction of inflammatory cytokines production by macrophages are important for clinical application.

• 한국자원식물학회지
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• 제24권5호
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• pp.604-612
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• 2011

씀바귀추출물이 LPS shock 염증반응에서 항염증효과에 미치는 영향을 검토하기 위하여 생체 및 세포배양실험에서 전염증성 cytokine들의 생성과 혈액 내 생물학적 수치를 조사했다. 그 결과 LPS 염증유도 rat에서 씀바귀 추출물은 혈액 내 전염증성 cytokines 들, 즉 IL-$1{\beta}$, IL-6 및 TNF-${\alpha}$의 생산을 저해하고, 한편으로는 IL-10의 생산을 촉진하였다. 간장 IL-$1{\beta}$ 및 IL-6의 농도는 씀바귀추출물 처리군이 대조군보다 유의하게 낮은 값을 나타내었으나, TNF-${\alpha}$ 및 IL-10의 농도는 모든 처리군 간에 유의한 차이를 나타내지 않았다. Raw 264.7 cell의 세포배양실험에서는 TNF-${\alpha}$의 농도가 유의한 차이를 나타내지는 않았지만, 3개 cytokine 모두가 씀바귀 투여량이 증가함에 따라 감소하는 경향을 보였다. IL-10의 농도는 씀바귀 처리군 들 모두가 높은 경향을 나타내었다. 혈액 내 total protein 및 albumin의 농도는 대조군과 유의한 차이를 나타내지는 않았으나, 씀바귀추출물 처리 군에서 높은 경향을 보였다. 이상의 결과들을 종합해 보면 씀바귀 추출물에는 항염증반응에 관여하는 기능성물질이 내재하고 있음을 시사해 준다.

• International Journal of Oral Biology
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• 제41권3호
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• pp.125-131
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• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• IMMUNE NETWORK
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• 제15권2호
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

• 한방재활의학과학회지
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• 제21권1호
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• pp.35-46
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• 2011

Objectives : The present study investigated inflammatory effect of Rheum undulatum L. in lipopolysaccharide-exposed rats and Raw 264.7 cells. Methods : Male rats weighting $185.39{\pm}8.21g$ fed basal diet for 1 week and 32 rats were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1time/1day) for 6 weeks. And we fed basal diet and administered an extract of Rheum undulatum L.(100 mg/kg, 200 mg/kg, 300 mg/kg, 1time/1day) to each experimental group of rats. We measured the plasma concentration of $IL-1{\beta}$($interleukin-1{\beta}$), IL-6 and $TNF-{\alpha}$(tumor necrosis $factor-{\alpha}$), liver cytokines, Raw 264.7 macrophages cytokines. Results : The plasma concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ peaked at 5h(hour) after LPS(lipopolysaccharides) injection, and the values of the Rheum undulatum L. extract groups were lower than those of the control group. In the increment of these cytokines concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Rheum undulatum L. extract groups were higher than those of the control group. In the increment of this cytokine concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver $IL-1{\beta}$ and IL-6 in the Rheum undulatum L. groups was lower than that of the control group. The concentrations of liver $TNF-{\alpha}$, and IL-10 showed no significant differences among all the treatment groups. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Rheum undulatum L. groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Rheum undulatum L. groups. Conclusions : These results indicate that the Rheum undulatum L. extracts have an functional material for inflammatory activities.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6491-6499
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• 2015

Background: Red-fleshed sweet orange juice (ROJ) comes from a new variety of citrus cultivated in Brazil that contains high levels of ${\beta}$-carotene and lycopene, and similar amounts of hesperidin (HSP) and nutrients, equivalently to blond orange juice (BOJ). Such bioactive compounds are associated with chemopreventive actions in several cancer cell lines. The purpose of this study was to examine the cytotoxicity, cell cycle, apoptosis, and cytokine secretion after BOJ, ROJ, and HSP treatment of a novel T acute lymphoblastic leukemia cell line, Loucy. Materials and Methods: Loucy cells were incubated for 24-h with BOJ, ROJ, and HSP, and the viability was measured using trypan blue. Cell cycling and apoptosis were assessed by propidium iodide (PI) and annexin V-FITC/PI flow cytometry, respectively. Secretion of cytokines $IL-1{\alpha}$, $IL1-{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-17A, $IFN{\gamma}$, $TNF{\alpha}$, $TGF{\beta}$, $MIP{\alpha}$, and $MIP{\beta}$ was determined by ELISA array. Results: BOJ and ROJ treatments promoted Loucy cell cytotoxicity. Additionally, BOJ induced cell cycle arrest in the G0/G1 phase, and decreased the cell accumulation in the G2/M. ROJ decreased only the G0/G1 fraction, while HSP did not change the cell cycle. BOJ led to apoptosis in a different fashion of ROJ, while the first treatment induced apoptosis by increase of late apoptosis and primary necrotic fractions, the second increased early and late apoptosis, and primary necrotic fraction compared to positive controls. HSP had no effect on apoptosis. IL-6 and IL-10 were abrogated by all treatments. Conclusions: Taking together, these results suggest potential chemopreventive effects of BOJ and ROJ on Loucy cells.

• Korean Journal of Acupuncture
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• 제26권3호
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• pp.43-54
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• 2009

Objectives : To investigate the anti-inflammatory effects of Prunella vulgaris pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods : Sprague-Dawley rats were divided into 5 groups; normal control (n=8), LPS control (n=8), LPS+Prunella vulgaris pharmacopuncture at CV4 (CV4, n=8), LPS+Prunella vulgaris pharmacopuncture at ST36 (ST36, n=8), and LPS+Prunella vulgaris pharmacopuncture at CV12 (CV12, n=8). Pharmacopuncture was given every two days for 4 weeks followed by inflammation induction by peritoneal LPS injection (5mg/kg). Proinflammatory cytokines including interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-10 (IL-10), thiobarbituric acid reactive substance (TBARS) from blood and liver tissue were compared before and 5 hrs after inflammation induction. Results : In CV4 and CV12 groups, plasma IL-$1{\beta}$, IL-6 and TNF-$\alpha$ levels increased by LPS injection, significantly decreased 5 hrs after injection (p<0.05). For CV12 group, plasma IL-10 concentration significantly increased (p<0.05). Liver IL-$1{\beta}$ and IL-6 levles significantly decreased in CV4 and CV12 groups (P<0.05), while normal and LPS control groups were not significantly different in TNF-$\alpha$ and IL-10 levels. Plasma TBARS concentration was significantly decreased in CV12 group, while there was no significant difference among LPS control and pharmacopuncture groups for liver TBARS concentration. Conclusions : Based on the present findings, Prunella vulgaris pharmacopuncture at CV12 may have a potentially preventive anti-inflammatory effect in an LPS-induced inflammatory rat model.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제8권2호
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• pp.89-94
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• 2004

The arterial pressure is regulated by the nervous and humoral mechanisms. The neuronal regulation is mostly carried out by the autonomic nervous system through the rostral ventrolateral medulla (RVLM), a key area for the cardiovascular regulation, and the humoral regulation is mediated by a number of substances, including the angiotensin (Ang) II and vasopressin. Recent studies suggest that central interleukin-1 (IL-1) activates the sympathetic nervous system and produces hypertension. The present study was undertaken to elucidate whether IL-1 and Ang II interact in the regulation of cardiovascular responses to the stress of hemorrhage. Thus, Sprague-Dawley rats were anesthetized and both femoral arteries were cannulated for direct measurement of arterial pressure and heart rate (HR) and for inducing hemorrhage. A guide cannula was placed into the lateral ventricle for injection of IL-1 $(0.1,\;1,\;10,\;20\;ng/2\;{\mu}l)$ or Ang II $(600\;ng/10\;{\mu}l)$. A glass microelectrode was inserted into the RVLM to record the single unit spike potential. Barosensitive neurons were identified by an increased number of single unit spikes in RVLM following intravenous injection of nitroprusside. I.c.v. $IL-1\;{\beta}$ increased mean arterial pressure (MAP) in a dose-dependent fashion, but HR in a dose-independent pattern. The baroreceptor reflex sensitivity was not affected by i.c.v. $IL-1\;{\beta}$. Both i.c.v. $IL-1\;{\alpha}\;and\;{\beta}$ produced similar increase in MAP and HR. When hemorrhage was induced after i.c.v. injection of $IL-1\;{\beta}$, the magnitude of MAP fall was not different from the control. The $IL-1\;{\beta}$ group showed a smaller decrease in HR and a lower spike potential count in RVLM than the control. MAP fall in response to hemorrhage after i.c.v. injection of Ang II was not different from the control. When both IL-1 and Ang II were simultaneously injected i.c.v., however, MAP fall was significantly smaller than the control, and HR was increased rather than decreased. These data suggest that IL-1, a defense immune mediator, manifests a hypertensive action in the central nervous system and attenuates the hypotensive response to hemorrhage by interaction with Ang II.