• Toxicological Research
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• 제22권3호
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• pp.245-251
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• 2006

Nitric oxide(nitrogen monoxide, NO) plays important physiological roles, but excessive generation can be toxic. NO is present in cigarette smoke at up to 1,000 ppm, and probably represents one of the greatest exogenous sources of NO to which humans are exposed. We investigated whether cigarette smoking reduces the production of endogenous NO and whether it influences the action of lipopolysaccharide(LPS) to induce nitric oxide synthase activity in mouse brain. Mice(C57BL6/J) were exposed to cigarette smoke for 8 weeks. LPS was injected intraperitoneally in single or combination with the exposure to cigarette smoke. Six hours after the injection of LPS, mice were sacrificed and sera and brains were collected. Serum concentrations of nitrate and nitrite were not charged by 4-week smoke exposure, but were significantly increased by 6 and 8 weeks of smoke exposure. Interestingly, cigarette smoke reduced the elevation in serum nitrate and nitrite concentrations produced by LPS after 4-week smoking exposure. NO synthase(NOS) activity in brain was upregulated by LPS-administration. However, cigarette smoke exposure remarkably and consistently decreased the LPS-induced activity in mouse brain. This result suggests that cigarette smoking may affect against overproduction of the endogenous NO by LPS through the inhibition of NOS activity induced by LPS in brain or by modulation of the LPS action for the induction of NOS activity. We also suggest the possibility that the exogenous NO evolved in cigarette smoke enables feedback inhibition of NOS activity or other possibility that it attenuates the toxicity of endotoxin LPS in vivo by unknown mechanisms, which should be further studied.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.263-268
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• 2015

5-Lipoxygenase (5-LO) plays a pivotal role in the progression of atherosclerosis. Therefore, this study investigated the molecular mechanisms involved in 5-LO expression on monocytes induced by LPS. Stimulation of THP-1 monocytes with LPS ($0{\sim}3{\mu}g/ml$) increased 5-LO promoter activity and 5-LO protein expression in a concentration-dependent manner. LPS-induced 5-LO expression was blocked by pharmacological inhibition of the Akt pathway, but not by inhibitors of MAPK pathways including the ERK, JNK, and p38 MAPK pathways. In line with these results, LPS increased the phosphorylation of Akt, suggesting a role for the Akt pathway in LPS-induced 5-LO expression. In a promoter activity assay conducted to identify transcription factors, both Sp1 and NF-${\kappa}B$ were found to play central roles in 5-LO expression in LPS-treated monocytes. The LPS-enhanced activities of Sp1 and NF-${\kappa}B$ were attenuated by an Akt inhibitor. Moreover, the LPS-enhanced phosphorylation of Akt was significantly attenuated in cells pretreated with an anti-TLR4 antibody. Taken together, 5-LO expression in LPS-stimulated monocytes is regulated at the transcriptional level via TLR4/Akt-mediated activations of Sp1 and NF-${\kappa}B$ pathways in monocytes.

• International Journal of Oral Biology
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• 제38권3호
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• pp.87-92
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• 2013

Periodontal inflammation increases the risk of tooth loss, particularly in cases where there is an associated loss of alveolar bone and periodontal ligament (PDL). Histological and morphometric evaluation of periodontal inflammation is difficult. Especially, the lengths of the periodontal ligament and interdental alveolar bone space have not been quantified. A quantitative imaging procedure applicable to an animal model would be an important clinical study. The purpose of this study was to quantify the loss of alveolar bone and periodontal ligament by evaluation with micro-computed tomography (micro-CT). Another purpose was to investigate differences in infections with systemic E. coli LPS and TNF-${\alpha}$ on E. coli lipopolysaccharide (LPS) in loss of alveolar bone and periodontal ligament model on mice. This study showed that linear measurements of alveolar bone loss were represented with an increasing trend of the periodontal ligament length and interdental alveolar process space. The effects of systemic E. coli LPS and TNF-${\alpha}$ on an E. coli LPS-induced periodontitis mice model were investigated in this research. Loss of periodontal ligament and alveolar bone were evaluated by micro-computed tomography (micro-CT) and calculated by the two- and three dimensional microstructure morphometric parameters. Also, there was a significantly increasing trend of the interdental alveolar process space in E. coli LPS and TNF-${\alpha}$ on E. coli LPS compared to PBS. And E. coli LPS and TNF-${\alpha}$ on E. coli LPS had a slightly increasing trend of the periodontal ligament length. The increasing trend of TNF-${\alpha}$ on the LPS-induced mice model in this experiment supports the previous studies on the contribution of periodontal diseases in the pathogenesis of systemic diseases. Also, our findings offer a unique model for the study of the role of LPS-induced TNF-${\alpha}$ in systemic and chronic local inflammatory processes and inflammatory diseases. In this study, we performed rapidly quantification of the periodontal inflammatory processes and periodontal bone loss using micro-computed tomography (micro-CT) in mice.

• 대한본초학회지
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• 제28권5호
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• pp.113-119
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• 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.

• 동의신경정신과학회지
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• 제33권3호
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• pp.277-285
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• 2022

Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

• 한국해양공학회:학술대회논문집
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• 한국해양공학회 2006년 창립20주년기념 정기학술대회 및 국제워크샵
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• pp.25-28
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• 2006

This paper dealt with the LPS process for the development of high performance SiC materials, based on the detailed analysis of their microstructure and mechanical properties. The submicron SiC powder was used for the fabrication of LPS-SiC materials. A mixture of $Al_2O_3$ and $Y_2O_3$ particles was also used as a sintering additive in the LPS process. LPS-SiC materials were fabricated at different temperatures, using various additive composition ratio ($Al_2O_3/Y_2O_3$). The total amount of additive materials ($Al_2O_3+Y_2O_3$) was fixed as 10 wt%. The characterization Of LPS-SiC materials was investigated by means of SEM, XRD and three point bending test. The LPS-SiC material represented a relative density of about 98 % and a flexural strength of about 800MPa, when it was fabricated at the temperature of $1820^{\circ}C$ and the additive compositional ratio of 1.5.

• 약학회지
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• 제43권1호
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• pp.48-54
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• 1999

Effects of zinc chloride (Zn) on the immune responses of lipopolysaccharide (LPS) were studied by using ICR mice. Mice were divided into 4 groups (10 mice/group), and Zn was given to the mice with i.p. injection at 0.3 mg/kg 5 times a week for 14 days, and 1 hr after Zn administration, LPS was given with i.p. injection at 5 mg/kg twice a week. Mice were immunized and challenged with sheep red blood cells (SRBC). Immunobiological responses were evaluated by humoral, cellular and nonspecific immunity. LPS treatment significantly increased the relative weights of spleen and thymus, hemagglutination titer (HA) and proliferation of splenocytes compared with those in controls, but significantly decreased the body weight gain. Zn treatment significantly increased proliferation of splenocytes and circulating leukocytes compared with those in controls. Combination of Zn and LPS significantly decreased the body weight gain and proliferation of splenocytes compared with those in controls. Combination of Zn and LPS significantly decreased HA and proliferation of splenocytes than in LPS alone. These findings indicate that zinc lowered the humoral immune responses of LPS.

• 생명과학회지
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• 제30권4호
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• pp.331-342
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• 2020

미세교세포(Microglial cells)에서 신경염증반응(neuroinflammatory responses)의 억제는 알츠하이머질환, 파킨슨질환, 헌팅턴질환과 같은 신경퇴행성질환(neurodegenerative diseases)을 치료하기 위한 주요 표적으로 고려되고 있다. 천문동(Asparagus cochinchinesis)은 열, 기침, 신장 질환, 유방암, 염증성질환 및 뇌질환을 치료하는 데 오랫동안 사용 되어온 전통 치료제(Traditional medicine)이다. 본 연구에서는 lipopolysaccharide (LPS)로 활성화된 BV-2 미세교세포에서 항염증효과가 있는 천문동 뿌리 열수추출물(Aqueous extract from A. cochinchinesis root, AEAC)의 신경보호 메커니즘을 연구하였다. 먼저, 어떤 유의적인 세포독성은 플라보노이드(flavonoid), 페놀(phenol), 사포닌(saponin)을 함유하는 AEAC를 4가지 농도로 처리된 BV-2세포에서 검출되지 않았다. 또한, nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA 및 inducible nitric oxide synthase (iNOS) mRNA 수준은 AEAC+LPS 처리군에서 비하여 21%정도 감소하였다. 전염증성 사이토카인(TNF-α과 IL-1β) 및 항염증성 사이토카인(IL-6와 IL-10)농도에 대한 유사한 감소는 비록 감소비율은 다르지만, Vehicle+LPS 처리군에 비해 AEAC+LPS 처리군에서 검출되었다. 더불어, LPS 처리 후 mitogen-activated protein (MAP) kinase의 인산화수준의 증가는 AEAC 전처리군에서 유의하게 회복되었고, 세포주기에서 G2/M의 억제(arrest)는 AEAC+LPS 처리군에서 개선되었다. 또한, LPS 처리로 유도된 ROS의 증가도 AEAC 전처리군에서 감소되었다. 따라서, 이러한 결과는 AEAC가 MAPK 신호전달 경로, 세포주기 및 ROS (reactive oxygen species) 생성의 조절을 통해 LPS 자극에 대한 항신경염증 활성을 유도함을 제시하고 있다.

• 한국수정란이식학회지
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• 제21권3호
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• pp.233-239
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• 2006

본 연구는 후산정체 젖소에 있어서 Lipopolysaccharide의 처리가 자궁 회복에 미치는 영향을 조사하기 위하여 2004년부터 2005년까지 2년간에 걸쳐 축산연구소와 전문 경영체 농장에서 사육중인 홀스타인 착유우 중 분만 후 12시간이 경과하여도 태반이 배출되지 않았던 후산정체우 33두를 대상으로 LPS $100{\mu}g$구, LPS $200{\mu}g$구 및 대조구 각각 11두씩을 공시하였으며 분만 후 20일째에 대조구는 PBS를, 처치구는 LPS를 자궁내에 주입하여 분만 후 40일째에 초음파 측정을 통하여 자궁의 크기 및 자궁내 삼출물의 저류 정도를 조사하여 다음과 같은 결과를 얻었다. 1.자궁각의 크기에 있어서 30 mm이하인 경우는 대조구 45.5%, LPS $100{\mu}g$구 100%, LPS $200{\mu}g$구 72.7%였고 $31{\sim}50mm$인 경우는 대조구 27.3%, LPS $100{\mu}g$구 0%, LPS $100{\mu}g$구 18.2%였으며 51 mm이상인 경우는 대조구 27.3%, LPS $100{\mu}g$구 0%, LPS $200{\mu}g$구 9.1%였다. 2. 삼출액의 저류 상태에 있어서 삼출액이 거의 없는 경우는 대조구 18.2%, LPS $100{\mu}g$구63.6%, LPS $200{\mu}g$구 54.6%였고 자궁강내에 삼출액이 소량 있는 경우는 대조구 36.4%, LPS $100{\mu}g$구 36.4%, LPS $200{\mu}g$구 36.4%였으며 자궁강내에 삼출액이 고여 있는 경우는 대조구 45.5%, LPS $100{\mu}g$구 0%, LPS $200{\mu}g$구 9.1%였다.

• 동국한의학연구소논문집
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• 제9권
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• pp.35-49
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• 2000

본 실험은 대방풍탕(大防風湯)이 혈관생성과 세포유착인자발현 억제를 통해 LPS(lipopolysaccharide)유발 관절염 완화에 미치는 영향을 조사하기 위해 LPS주사로 관절염이 유발된 생쥐에게 대방풍탕(大防風湯) 추출액을 음용 투여하였다. 실험동물은 20g된 female Balb/c계 생쥐암컷을 선별하여 아무런 처치를 하지 않은 대조군, 무릎관절에 LPS를 주사한 LPS군, LPS주사후 대방풍탕(大防風湯) 추출액을 투여한 DBP군으로 나누어, 다시 LPS와 DBP군은 LPS처리 후 시간의 경과에 따라 3, 7, 14일로 구분하였으며, 실험군 각각에는 실험동물을 10마리씩 배정하였다. 광학 현미경(BX50)으로 대방풍탕(大防風湯) 추출액 투여가 LPS주사 후 증가된 윤활 관절막내 혈관분포 증가에 미치는 영향과 아울러 윤활세포, 섬유화 및 섬유모세포, 비만세포와 염증관여세포, 세포유착인자 등의 윤활 관절막에서의 형태변화를 관찰하였다. DBP군에서는 자유면에서 윤활세포과형성의 억제와 침윤 림프구의 감소, 낮은 섬유화 양상과 침적 섬유모세포의 감소, 모세혈관 주변의 림프구 침적 감소와 비만세포 분포감소, 자유면과 섬유지역분포ICAM과 혈관주변분포VCAM 등과 같은 세포유착인자의 감소 등이 관찰되었다. 이상의 결과로 볼 때 대방풍탕(大防風湯)은 관절염 유발시 발생되는 혈관생성과 세포유착인자의 발현증가 등을 억제함으로써 이후 발생되는 윤활 관절막 손상을 완화하는 것으로 사료된다.