• Nutrition Research and Practice
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• v.8 no.5
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• pp.501-508
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• 2014

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and NO and $PGE_2$ productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-${\kappa}B$ and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-${\kappa}B$ activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and $PGE_2$ productions. RE and RH treatments reduced IL-$1{\beta}$ and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-${\kappa}B$ and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Korean Journal of Biological Psychiatry
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• v.10 no.1
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• pp.70-79
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• 2003

Object : Currently, the alteration of cytokine system has been known to play an important role in regard to depressive symptom. We focused on the relationship between immunological parameters and clinical improvement in major depressive disorder. Method : Data were collected on 26 patients with major depressive disorder using a 8-week prospective follow-up design. After 8-week treatment period with fluoxetine, patients were classified into a response group and a non-response group according to their psychopathological outcome as evaluated by Hamilton Depression Rating Scale. The differences of the immunological parameters between pre-treatment phase and post-treatment phase were compared among patients. The difference of those was also compared within each phase among them. The relationship between socio-demographic variables, depression, cytokine, mononuclear cells was examined by correlation analysis. Multiple regression analyses were performed to explore the predictors of clinical improvement of major depressive disorder. Result : Pre-treatment levels of IL-$1{\beta}$ in the response group were significantly higher than those in the non-response group. Pre-treatment levels of IL-$1{\beta}$ of all patients and in the response group were positively correlated with pre-treatment monocyte counts. Patients with subsequent remission showed significantly lower IL-6 values at baseline than those with non-response. Post-treatment values of IL-6 did not differ significantly among the patients. The correlation test showed more frequent relations among cytokines and mononuclear cells in the response group than in the non-responder group. Especially, serum level of IL-6 in pre-treatment phase was only significantly correlated with HAMD score after 8-week treatement phase, while other cytokines and mononuclear cells were not. Pretreatment level of IL-6 was of paramount importance in predicting clinical improvement of depressive symptom. Conclusion : The immune system of major depressive disorder patients might dichotomize the patients into subsequent responders and non-responders. Immune system might be of great influence on the clinical improvement of major depressive disorder. The mode of interaction between depression and cellular immune function and the mediators responsible for the cytokine production need to be studied further.

• BMB Reports
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• v.47 no.9
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• pp.512-517
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• 2014

In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.601-611
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• 2001

Objectives : We aimed to identify the dose-dependent inhibitory effects of Cheonsagunja-tang(喘四君子湯), leech(Hirudo medicinalis/水蛭) roasted with Ephedrae Herba(麻黃) on the mRNA expression of IL-6, IL-16, GM-CSF involved in the asthma model. Methods : In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor(TNF)-${\alpha}$ for artificial inflammatory expression. ${\beta}$-actin messenger RNA(mRNA) was used by internal standard. After 24 hours of the Cheonsagunja-tang, leech-treatment, total cellular RNAs were collected treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 16 and GM-CSF were measured by RT-PCR with electrophoresis. Results: In the Cheonsagunja-tang study, the mRNA expression of IL-6 showed 30% transcriptional inhibitory effect compared to the control group in the $100{\mu}l/ml$ category(p<0.005). In the IL-16, there was 26%, 31% and 31% transcriptional inhibitory effect compared to the control groups in the $4{\mu}l/ml$, $20{\mu}l/ml$ and $100{\mu}l/ml$ categories, respectively(p<0.05). In the GM-CSF, the experimental group had 56% transcriptional inhibitory effect compared to the control group in the $100{\mu}l/ml$ category(p<0.001). In other concentrations, there was no inhibitory effect. In the leech study, the mRNA expression of IL-6 showed 37% transcriptional inhibitory effect compared to the control group in the $100{\mu}l/ml$ category(p<0.001). In the IL-16, there was 63% and 67% transcriptional inhibitory effect compared to the control groups in the $20{\mu}/ml$ and $100{\mu}/ml$ categories, respectively(p<0.001). In the GM-CSF, there was 64% and 68% transcriptional inhibitory effect compared to the control groups in the $20{\mu}l/ml$ and $100{\mu}l/ml$ categories, respectively(p<0.001). In other concentrations, there was no inhibitory effect. Conclusions : This study shows that Cheonsagunja-tang and leech roasted with Ephedrae Herba have dose-dependent inhibitory effects on the mRNA expression of IL-6, IL-16 and GM-CSF in BEAS-2B cell lines, human epithelial cells.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.345-360
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• 2011

Objectives : This study was examined to investigate the effects of Cheonmagudeng-um gagam (CGG) extract on spontaneous hypertension. Methods : For the study of CGG, we divided rats into three groups. The normal group was Wister Kyoto rats (WKY). The control group was spontaneously hypertensive rats (SHR). The treatment group was SHR which were administered CGG extract (SHR-CGG). SHR-CGG were orally administered CGG extract that was diluted in distilled water at the various concentrations for 4 weeks (234.5 mg/kg) and SHR were orally administered the same dosage of plain distilled water as SHR-CGG. Then we measured anti-oxygen effects, ACE inhibitory activity, weight of heart and kidney, blood pressure, heart rate, plasma aldosterone, electrolyte, creatinine, uric acid, BUN, and observed the cortex of the cardiac muscle, kidney, and adrenal gland. Results : CGG increased DPPH scavenging activity and SOD similar activity depending on the concentration. CGG significantly decreased ROS, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, heart weight, blood pressure, heart rate, aldosterone, and BUN in SHR. CGG increased ACE inhibition activity depending on the concentration. CGG inhibited the heart, kidney and adrenal gland tissue injury that is caused by hypertension. Conclusions : These results suggest that CGG is effective in treatment and prevention of hypertension.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.479-487
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• 2016

Recently, various marine algae have been considered as a natural resource for anti-inflammation. In this research, we investigated the anti-inflammatory activity of Ulva pertusa Kjellman ethanol extract (UPKEE). This study showed that UPKEE inhibited the secretion of cytokines including IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$, and reduced the expression of $NF-{\kappa}B$ and mitogen-activated protein kinases (MAPKs) as well as iNOS and COX-2. In the formation of mouse ear edema test, three doses (10, 50, 250 mg/kg body weight) of UPKEE showed inhibitory activity after inducing inflammation using croton oil. In conclusion, we found that UPKEE showed an inhibitory effect on $NF-{\kappa}B$ and MAPKs, and reduced the secretion of inflammatory cytokines. This result suggests that UPKEE can be used as a natural anti-inflammatory resource in food industry.

• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.342-347
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• 2007

The dried fruit of the Rubus coreanus, which is well-known in Korea and referred to as 'Bokbunja,' has been employed as a traditional medicine for centuries. This crude drug has been utilized in Korea for the management of impotence, spermatorrhea, enuresis, asthma, and allergic diseases. Our previous study demonstrated that the ethanol extracts of R. coreanus have anti-inflammatory effects. The principal objective of the present study was to conduct a comparison of the anti-inflammatory effects of the ethanol extracts of R. coreanus and R. occidentalis; here, we tested the unripe (URCE), half-ripened (HRCE), and ripened fruits (RCE) of R. coreanus, and the unripe (UROE), half-ripened (HROE), and ripened fruits (ROE) of R. occidentalis. We found that URCE, UROE, HRCE, and HROE reduced the production of nitric oxide and prostaglandin $E_{2}$ as well as pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 murine macrophages. Interestingly, the R. coreanus extracts showed stronger inhibitory effects on the production of these inflammatory mediators than the R. occidentalis extracts.

• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1159-1166
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• 2013

Orientia tsutsugamushi, a gram-negative bacterium, causes severe acute febrile illness in humans. Despite this danger, the route of infection, infectivity, and protective mechanisms of the host's immune response to O. tsutsugamushi are unclear. Dendritic cells (DCs) are one of the most important cell types in bridging the innate and adaptive immune responses. In this study, we observed that O. tsutsugamushi infects and replicates in monocyte-derived DCs (MODCs). During infection and replication, the expressions of the cytokines IL-12 and TNF-${\alpha}$, as well as the co-stimulatory molecules CD80, CD83, CD86, and CD40, were increased in MODCs. When O. tsutsugamushi-treated MODCs were co-cultured with autologous $CD4^+$ T cells, they enhanced production of IFN-${\gamma}$, a major Th1 cytokine. Collectively, our results show that O. tsutsugamushi can replicate in MODCs and can simultaneously induce MODC maturation and increase proinflammatory cytokine levels in MODCs that subsequently activate $CD4^+$ T cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.607-616
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• 2018

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of $TNF-{\alpha}$ was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.7
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• pp.1021-1028
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• 2012

Peripheral blood mononuclear cells (PBMCs) discriminate microbial pathogens and induce T-cell responses of appropriate effector phenotype accordingly. Toll-like receptors (TLRs), in part, mediate this microbial recognition and differentiation while the development of T-cell effector functions critically depends on the release of Th1- or Th2- type cytokines. In the present study, buffalo PBMCs were stimulated under in vitro culture conditions by Bacillus subtilis cell wall petidoglycan, a TLR2 ligand, in a dose- and time- dependent manner. The expression of TLR2 as well as the subsequent differential induction of the Th1 and Th2 type cytokines was measured. Stimulation was analyzed across five doses of peptidoglycan ($10{\mu}g/ml$, $20{\mu}g/ml$, $30{\mu}g/ml$, $40{\mu}g/ml$ and $50{\mu}g/ml$) for 3 h, 12 h, 24 h and 36 h incubation periods. We observed the induction of TLR2 expression in a dose- and time-dependent manner and the peptidoglycan induced tolerance beyond $30{\mu}g/ml$ dose at all incubation periods. The correlation between peptidoglycan stimulation and TLR2 induction was found positive at all doses and for all incubation periods. Increased production of all the cytokines was observed at low doses for 3 h incubation, but the expression of IL-4 was relatively higher than IL-12 at the higher antigen doses, indicating tailoring towards Th2 response. At 12 h incubation, there was a pronounced decrease in IL-4 and IL-10 expression relative to IL-12 in a dose- dependent manner, indicating skewing to Th1 polarization. The expression of IL-12 was highest for all doses across all the incubation intervals at 24 h incubation, indicating Th1 polarization. The relative expression of TNF-${\alpha}$ and IFN-${\gamma}$ was also higher while that of IL-4 and IL-10 showed a decrease. For 36 h incubation, at low doses, relative increase in the expression of IL-4 and IL-10 was observed which decreased at higher doses, as did the expression of all other cytokines. The exhaustion of cytokine production at 36 h indicated that PBMCs became refractory to further stimulation. It can be concluded from this study that the cytokine response to sPGN initially was of Th2 type which skews, more pronouncedly, to Th1 type with time till the cells become refractory to further stimulation.