• 한국자원식물학회지
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• 제33권6호
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• pp.638-644
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• 2020

Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

• KSBB Journal
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• 제28권1호
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• pp.7-12
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• 2013

Thromboxane $A_2$ ($TXA_2$) is one of major proinflammatory mediators, plays an important role in the development of vascular inflammatory diseases. $TXA_2$ acting through the thromboxane receptor regulates multiple pathways and genes in a variety of cells. In this study, we report that the activation of thromboxane receptor with U46619 increases the interleukin-8 (IL-8) mRNA in vascular endothelial cells. We also demonstrated that U46619 produces the activations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK), which is required for endothelial IL-8 production. And U46619 enhanced mRNA stability of IL-8 transcripts in endothelial cells. Moreover, inhibition of ERK1/2 or p38MAPK reduced monocyte adhesion to aortic endothelium stimulated by U46619. Therefore, these results suggest that activation of thromboxane receptor promotes the expression of IL-8 via ERK1/2 and p38MAPK activation in endothelial cells.

• 생물정신의학
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• 제3권1호
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• pp.109-114
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• 1996

정신분열증에서 interleukin의 변화는 그 질환에서의 면역학적 가설의 부가적인 증거로 제시되어 왔다. 본 연구에서는 quantitative "sandwich" ELISA 법을 이용하여 26명의 정신분열증 환자를 대상으로 연령을 상응시킨 정상대조군과 비교해 IL-$1{\beta}$, IL-2, IL-6 농도의 차이가 있는지 알아보았다. 또한 정신분열증 환자에서 IL농도와 양성증상 및 음성증상, 연령, 유병기간 등의 임상변인과의 상관관계를 조사하여 다음과 같은 결론을 얻었다. 1) 정신분열증군이 정상대조군보다 IL-2 농도의 유의한 중가를 나타내었으며, IL-$1{\beta}$와 IL-6는 유의한 차이가 없었다. 2) 정신분열증군에서 IL-2, IL-6와 음성증상간의 유의한 상관관계가 있었다. 본 연구는 정신분열증의 연역학적 가설을 지지하고 있으며, IL은 정신분열증의 음성증상에 관련된다고 생각된다. 앞으로 국내에서도 이러한 환자들의 임상적 특징, 진단, 치료에 관심을 갖아야 할 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• 제38권2호
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• pp.98-102
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• 2011

Objective: To investigate the effects of pioglitazone on controlled ovarian stimulation (COS), IVF outcomes, and follicular fluid (FF) cytokine concentrations in patients with polycystic ovary syndrome (PCOS). Methods: Eighty-six infertile patients with PCOS resistant to clomiphene citrate were randomized to receive pioglitazone (30 mg/day) or placebo on the starting day of oral contraceptive (OC) pretreatment, followed by an IVF protocol using a GnRH antagonist. Pioglitazone or placebo was administered once daily from the starting day of OC to the day of hCG injection. Results: Total dose and days of recombinant follicle-stimulating hormone administered, and the numbers of retrieved and mature oocytes, were significantly lower in the pioglitazone group than in the control group. FF tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) concentrations at oocyte retrieval were also significantly lower in the pioglitazone group. The clinical pregnancy rate was higher and the incidence of severe ovarian hyperstimulation syndrome was lower in the pioglitazone group, but the differences were not statistically significant. Conclusion: Pioglitazone reduces FF TNF-${\alpha}$ and IL-6 levels, and may improve ovarian response to COS in patients with PCOS.

• Archives of Pharmacal Research
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• 제29권11호
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• pp.969-976
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• 2006

Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

• 생명과학회지
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• 제15권4호
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• pp.595-599
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• 2005

무(한국 품종 및 일본 품종)를 사용하여 H. pylori에 의한 위세포독성 및 IL-8생성에 미치는 영향을 살펴보았다. 그 결과 무는 H. pylori에 의한 위세포독성을 농도의존적으로$(2\~10 mg/ml)$ 억제하였으며 또한 위암세포인 KATO III에서 분비되는 IL-8의 생성을 억제시킴$(5\~10mg/ml)$을 알았다. 이러한 사실은 무가 H. pylori감염에 의한 위점막세포의 손상을 방지할 수 있음을 나타낸다.

• Journal of Microbiology and Biotechnology
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• 제16권10호
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• pp.1605-1612
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• 2006

Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.377-384
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• 1998

Gold compounds depress phagocytic cell responses, including chemotaxis, and respiratory burst. However, the effects of gold compounds on the function of phagocytic cells are variable according to the preparation of medicine. In this study, effect of tetrachloroauric acid on activated neutrophil responses, including respiratory burst, lysosomal enzyme release and change of intracellular $Ca^{2+}$ level and on the synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by macrophages was studied. This study further examines how gold compounds affect the activation processes. The respiratory burst stimulated by complement C5a, degraded IgG and PMA in neutrophils was inhibited by tetrachloroauric acid. In contrast to C5a and degraded IgG, PMA-stimulated superoxide production was weakly inhibited by tetrachloroauric acid. Staurosporine, genistein, EGTA and verapamil inhibited superoxide and $H_2O_2$ production caused by C5a and degraded IgG. PMA-stimulated superoxide production was inhibited by staurosporine but was not affected by genistein. Tetrachloroauric acid, genistein, EGTA and verapamil inhibited the release of acid phosphatase and myeloperoxidase, while the effect of staurosporine was not detected. The synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by $interleukin-1{\beta}$ in macrophages was inhibited by tetrachloroauric acid. Preincubation with tetrachloroauric acid, genistein, EGTA and verapamil, the elevation of [$Ca^{2+}_i$] evoked by C5a was inhibited. Store-regulated $Ca^{2+}$ entry in thapsigargin-pretreated neutrophils was decreased by the addition of tetrachloroauric acid and genistein. The effect of staurosporine on intracellular $Ca^{2+}$ mobilization was not observed. In conclusion, tetrachloroauric acid may suppress neutrophil responses through its inhibitory action on elevation of intracellular $Ca^{2+}$ level and protein kinase C. It might exhibit an inhibitory effect on the action of protein tyrosine kinase. Tetrachloroauric acid depresses cytokine production by macrophages.

• The Korean Journal of Physiology and Pharmacology
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• 제6권5호
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• pp.269-274
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• 2002

A large number of factors such as osteotropic hormones, cytokines, or growth factors are related to the bone remodeling which is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Recent investigations have indicated that cytokines such as $interleukin-1{\beta}\;(IL-1{\beta})$ and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ play a potential role in the bone resorption associated with a variety of pathological conditions such as inflammatory osteolytic disease. Collagen is the most abundant protein of the extracellular matrix of bone, and the participation of collagenase in bone resorption has been widely investigated. In this study, effects of $IL-1{\beta}$ and $TNF-{\alpha}$ on the release of collagenase from osteoblastic cells were measured. The gelatinase activity was also measured by gel substrate analysis (zymography) after electrophoresis of conditioned media of osteoblastic cell culture. $IL-1{\beta}$ increased the collagenase activity in ROS17/2.8 and HOS cell culture. $TNF-{\alpha}$ also increased the collagenase activity of osteoblastic cells. When two kinds of cytokines were treated simultaneously in the culture of osteoblastic cells, synergistic increase of collagenase activity was seen in ROS17/2.8 cells. $IL-1{\beta}$ and $TNF-{\alpha}$ significantly increased the collagenase activity after 6 hour treatment in the osteoblastic cell culture, and there was no additional increase according to the culture period. Osteoblastic cells released the gelatinase and molecular weight of this enzyme was measured about 70 KDa as assessed by zymogram. $IL-1{\beta}$ and $TNF-{\alpha}$ showed increase of the gelatinase activity produced by ROS17/2.8 and HOS cells. Taken together, this study suggested that $IL-1{\beta}$ and $TNF-{\alpha}$ can modulate bone metabolism, at least in part, by increased release of collagenase and gelatinase from osteoblasts.

• The Korean Journal of Physiology and Pharmacology
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• 제11권6호
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• pp.263-267
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• 2007

We have previously demonstrated that the level of leukocytes and neutrophils significantly increased immediately and 30 min after exercise. Interleukin-8 (IL-8) is an inflammatory cytokine that acts as a chemokine on neutrophils. In the present study, we evaluated the correlation between the number of neutrophils and leukocytes, and between the number of neutrophils and plasma IL-8 level. Long-distance trained runners (TRs, n = 10) and untrained sedentary control subjects (SEDs, n = 10) ran for one hour at 70% of heart rate reserve. In the TR, the number of neutrophils correlated significantly with the number of leukocytes in the blood. However, there was no correlation between the number of neutrophils and the plasma IL-8 concentration in both groups. Expressions of IL-8 protein and mRNA were markedly higher in the TRs as compared to the SEDs at three time intervals (pre-exercise, immediately after exercise, and post exercise). In conclusion, our results show that 1) the neutrophil level was dependent on the level of leukocytes 2) there was no correlation between the neutrophils count and plasma IL-8 concentration and 3) a higher plasma IL-8 level in athletes may be a unique characteristic of intensive training.