• 대한치과보존학회:학술대회논문집
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• 대한치과보존학회 2003년도 제120회 추계학술대회 제 5차 한ㆍ일 치과보존학회 공동학술대회
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• pp.550-550
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• 2003

IL-1${\alpha}$ and TNF-${\alpha}$ play an important role in initiating and coordinating the cellular events that make up the immune response to infection. The purpose of this study was to examine the effects of proinflammatory cytokines on mineralization and HO-1 protein expression in the human pulp cells. Human pulp cell cultures between the fifth and sixth passage were used in this study. Alkaline phosphatase and osteonectin were selected as markers for mineralization that is, odontoblast-like differentiation.(omitted)

• Tuberculosis and Respiratory Diseases
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• 제45권3호
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• pp.553-564
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• 1998

연구배경: LPS에 대한 숙주의 초기반응은 proin-flammatory cytokines의 분비이다. 이러한 "초기 반응" cytokines는 인지세포에서 표적세포 등에 신호를 전달하여 다른 대식세포를 포함한 면역세포, 폐장내 간엽성 세포들을 자극하여 화학주성인자, 성장인자, 유착분자 등의 발현을 증폭시키게 되면서 전염증단계가 정열하게된다. 내독소유발 급성폐손상에서 폐장내 proinflammatory cytokine 기원 세포들은 활성화된 대식세포/단핵구 외에 폐조직으로 유입된 동원 호중구의 역할이 중요하게 인식되고 있으며 이외에도 간엽성 세포들에서도 발현되고 있는 것으로 밝혀지고 있다. 저자들은 실험 백서에서 내독소를 정백내 주입하여 유발시킨 급성폐손상에서 proinflammatory cytokines인 TNF-$\alpha$ 및 IL 6 기원의 주된 세포(들)를 규명해 보고자 하였다. 방 법: 체중 $250{\pm}50g$의 건강체인 웅성 Sparague-Dawley를 정상 대조군(Normal Control Saline Group)과 내독소유발 급성폐손상군으로 분류하였으며 급성폐손상군은 백혈구결핍 내독소군(CPA-ETX Group)과 대조-내독소군(ETX Group)으로 하였다. 실험백서를 phenthotal sodium으로 마취한 후 생리식염수 0.4ml(control) 혹은 동량의 생리식염수에 용해시킨 LPS (055 : B5 E. coli, Sigma Chemical Co., St. Louis, MO), 5mg/kg를 백서 미부정맥으로 주사한 후 각각 0 및 3, 6 시간에 회생시켰다. 백혈구결핍 내독소군은 cyclophophamide, 7mg/kg를 복강내 주입하여 5 일째에 LPS를 같은 방법으로 주입하여 3, 6시간에 각각 희생시켰다. 각군에서 기관지폐포세척술을 전술한 바와 같이 시행하여 총백혈구수, 분획세포수 및 총단백량을 산출하였고 기관지폐포세척 TNF-$\alpha$ 및 IL 6를 생물학적 방법으로 각각 측정하여 비교하였다. 동시에 기관지폐포세척술을 하지 않은 정상대조군 및 대조-내독소군에서 TNF-$\alpha$ 및 IL 6 단백에 대한 면역조직화학염색을 시행하였다. 결 과: 기관지폐포세척 세포 및 단백량 측정 결과 정상대조군에 비해 대조-내독소군에서 기관지폐포세척 총백혈구수는 3, 6 시간째에 각각 유의한 증가를 보였으나 (p<0.01), 백혈구결핍 내독소군과는 차이가 없었다. 대조-내독소군은 정상대조군에 비해 기관지폐포세척단핵구 및 호중구수가 3, 6 시간째에 각각 유의하게 증가하였으며 (p<0.05) 특히 호중구 분획율의 유의한 증가를 동반하였다(p<0.05). 백혈구결핍 내독소군은 정상대조군에 비해 3, 6시간째에 각각 기관지폐포세척 호중구수 및 호중구분획율의 유의한 감소를 보였으나 (p<0.05) 기관지폐포세척 단핵구수 및 단핵구 분획율에서는 양군간에 차이가 없었다. 기관지폐포세척 총단백량은 내독소군에서 3, 6시간째에 각각 정상대조군에 비해 유의한 증가를 보였으며(p<0.05) 내독소군간에는 6시간째에 대조-내독소군에서 백혈구결핍 내독소군에 비해 유의하게 높았다(p<0.05). 기관지폐포세척 TNF-$\alpha$ 및 IL-6의 농도는 정상대조군에서 각각 $0.06{\pm}0.06$ U/ml(n=5) 및 $0.45{\pm}0.23$ U/ml(n=5)이었다. 내독소군에서 TNF-$\alpha$와 IL-6는 정상대조군에 비해 유의하게 상승되었으며 (p<0.05), 백혈구결핍 내독소군과 대조-내독소군간에 차이는 없었다. 면역조직화학염색결과 내독소 정맥 주입 3시간 및 6시간후의 폐조직에서 TNF-$\alpha$ 및 IL-6 단백이 폐포대식세포와 간질대식세포들에서 강하게 염색되는 소견을 관찰할 수 있었다. 결 론: 내독소혈증 유발 급성 폐손상의 초기 손상에 중요한 역할을 하는 proinflammatory cytokine의 주된 기원세포는 활성화된 폐포대식세포/단핵구세포들일 것으로 사료되며 이들 세포가 내독소혈증 유발 급성폐손상 발생에 주도적인 역할을 할 것으로 사료되었다.

• Natural Product Sciences
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• 제13권3호
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• pp.207-213
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• 2007

Scutellaria baicalensis is known as a herbal medicine with anti-inflammatory and anti-oxidative activities. However, effect of Scutellaria baicalensis on lupus pathogenesis that is characterized by overproduction of proinflammatory cytokines and abnormalities in regulation, function, and interaction of immune cells remains unclear. We investigated effects of Scutellariae radix methanol extract (SBMeOH) on the production of proinflammatory cytokines and abnormal activation of T cells in vitro in pristane-induced lupus BALB/c mice. These results demonstrated that SBMeOH significantly decreased the LPS-stimulated production of $TNF-{\alpha}$, IL-6, and IL-10 by splenic and peritoneal macrophages and IL-6 and IL-10 by splenocytes from pristane-induced lupus mice. SBMeOH significantly downregulated the Con A-stimulated overproduction of IL-6, IL-10, and $IFN-{\gamma}$ by splenocytes from pristane-induced lupus mice. Also, SBMeOH significantly attenuated the Con A-induced expression of CD4+ T cells and CD69+CD4+ T cells but not CD8+ T cells in pristane-induced lupus mice. Our findings indicate that SBMeOH may ameliorate lupus pathogenic inflammation and autoimmunity via downregulation of proinflammatory cytokine production and abnormal activation of T cells.

• 생약학회지
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• 제42권4호
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• pp.348-353
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• 2011

The aim of the present study is to investigate the cytokine production inhibitory effect of a Dictamni Radicis Cortex (DRC). DRC has been commonly used as important medicinal herb in China and it used to control eczema, atopic dermatitis, fever and inflammatory diseases. Inflammation, such as a bacterial infection in vivo metabolites, such as external stimuli or internal stimuli to the defense mechanisms of the biological tissue a variety of intracellular regulatory factors deulin inflammatory TNF-${\alpha}$, IL-$1{\beta}$, IL-6, IL-8, such as proinflammatory cytokines, prostagrandin, lysosomal enzyme, free radicals are involved in a variety of mediators. The present study was designed to determine the effect of the DRC on proinflammatory factors such as NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 in lipopolysaccharide (LPS) - stimulated RAW264.7 cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of DRC, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, the DRC reduced NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 production without cytotoxicity. Our results suggest that the DRC may have an anti-inflammatory property through suppressing inflammatory mediator productions.

• IMMUNE NETWORK
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• 제11권2호
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• pp.123-133
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• 2011

Background: Mycobacterium tuberculosis (Mtb) heparin binding hemagglutinin (HBHA) is an Ag known to evoke effective host immune responses during tuberculosis infection. However, the molecular basis of the host immune response to HBHA has not been fully characterized. In this study, we examined the molecular mechanisms by which HBHA can induce the expression of proinflammatory cytokines in macrophages. Methods: HBHA-induced mRNA and protein levels of proinflammatory cytokines were determined in bone marrow-derived macrophages (BMDMs) using RT-PCR and ELISA analysis. The roles of intracellular signaling pathways for NF-${\kappa}B$, PI3-K/Akt, and MAPKs were investigated in macrophage proinflammatory responses after stimulation with HBHA. Results: HBHA robustly activated the expression of mRNA and protein of both TNF-${\alpha}$ and IL-6, and induced phosphorylation of NF-${\kappa}B$, Akt, and MAPKs in BMDMs. Both TNF-${\alpha}$ and IL-6 production by HBHA was regulated by the NF-${\kappa}B$, PI3-K, and MAPK pathways. Furthermore, PI3-K activity was required for the HBHA-induced activation of ERK1/2 and p38 MAPK, but not JNK, pathways. Conclusion: These data suggest that mycobacterial HBHA significantly induces proinflammatory responses through crosstalk between the PI3-K and MAPK pathways in macrophages.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• BMB Reports
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• 제46권11호
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• pp.544-549
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• 2013

High mobility group box 1 (HMGB1) is involved in the pathogenesis of vascular diseases. Unlike activated protein C (APC), the activation of PAR-1 by thrombin is known to elicit proinflammatory responses. To determine whether the occupancy of EPCR by the Gla-domain of APC is responsible for the PAR-1-dependent antiinflammatory activity of the protease, we pretreated HUVECs with the PC zymogen and then activated PAR-1 with thrombin. It was found that thrombin downregulates the HMGB1-mediated induction of both TNF-${\alpha}$ and IL-6 and inhibits the activation of both p38 MAPK and NF-${\kappa}B$ in HUVECs pretreated with PC. Furthermore, thrombin inhibited HMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion molecules in HUVECs if EPCR was occupied. Collectively, these results suggest the concept that thrombin can initiate proinflammatory responses in vascular endothelial cells through the activation of PAR-1 may not hold true for normal vessels expressing EPCR under in vivo conditions.

• 생약학회지
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• 제40권3호
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• pp.233-237
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• 2009

Lindera obtusiloba has been used for centuries as a traditional medicine in Korea and recently known to have an anti-fibrotic effect. In this report, we investigated the effect of hot water extract from L. obtusiloba (WELB) on the mast cell-mediated allergic inflammation and studied its possible mechanisms of action. WELB inhibited phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced histamine release in HMC-1 human mast cells. WELB reduced PMACI-induced gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-$\alpha$, interleukin (IL)-$1{\beta}$, IL-6, and IL-8. The inhibitory effect of WELB on the expression of proinflammatory cytokines was c-jun N-terminal kinase and nuclear factor-${\kappa}B$ dependent. These results indicate that WELB may be beneficial in the treatment of mast cell-mediated allergic inflammation.

• Journal of Acupuncture Research
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• 제27권2호
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• pp.59-69
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• 2010

Objectives : This study was designed to investigate effects of Lumbricus pharmacopuncture (LP) on the lipid lowering, anti-oxidative activity and concentration of proinflammatory cytokines in rat fed high fat diet. Methods : Sprague-Dawley male rats were fed high fat diet for 8 weeks and experimental groups were divided into 4 groups as follows : Control, Lumbricus Jungwan ($CV_{12}$) pharmacopuncture (T I), Lumbricus Joksamni ($ST_{36}$) pharmacopuncture (T II), Lumbricus Jungwan ($CV_{12}$) and Joksamni ($ST_{36}$) pharmacopuncture (T III). Results : The levels of plasma FFA, TG, total cholesterol, LDL-C, TBARS, IL-$1{\beta}$, IL-6, TNF-$\alpha$ and liver total cholesterol, TG, TBARS, SOD, catalase, IL-6 in more than one LP group were significantly lower than those of Control groups. The level of IL-10 in one of LP groups was significantly higher than that of Control group. Conclusions : As the results were shown, LP treatment have considerable effects on lipid lowering, anti-oxidative activity and concentration of proinflammatory cytokines in rat fed high fat diet.

• 약학회지
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• 제60권1호
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• pp.21-28
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• 2016

Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.