• Fisheries and Aquatic Sciences
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• v.14 no.4
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• pp.267-274
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• 2011

Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-${\kappa}B$). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and $PGE_2$ production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-${\kappa}B$ in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-${\kappa}B$ p65 subunit by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that the CFE-mediated inhibition of NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells is mediated through the NF-${\kappa}B$-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.40-48
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• 2016

The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against $CCl_4$-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating $CCl_4$-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of $I{\kappa}B{\alpha}$ through binding of $I{\kappa}B{\alpha}$. Inhibition of NF-${\kappa}B$ activity by NF-${\kappa}B$-specific suppressor $I{\kappa}B{\alpha}$ is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.171.2-171.2
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• 2003

Retinoids have been shown to be effective in suppressing tumor development in chemical carcinogens such as N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) induced mammary tumors in various animals. However, retinoids-mediated chemopreventive process, linked to transcription factor NF-kappaB activation on chemoprevention has yet to be studied. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1365-1370
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• 2012

The high mobility group box-1 (HMGB1) protein and NALP3 inflammasome have been identified to play important roles in inflammation and cancer pathogenesis, but the relationships between the two and cancer remain unclear. The current study investigated the relationship between HMGB1 and the NALP3 inflammasome in THP-1 macrophages. HMGB1 was found unable to activate the NALP3 inflammasome and failed to induce the release of the IL-$1{\beta}$ and IL-18 in THP-1 macrophages. HMGB1 was also found significantly enhanced the activity of ATP to induce IL-$1{\beta}$ and IL-18 by the induction of increased expression of pro-IL-$1{\beta}$ and pro-IL-18. This process was dependent on activation of RAGE, MAPK p38 and NF-${\kappa}B$ signaling pathway. These results demonstrate that HMGB1 promotes the synthesis of pro-IL-$1{\beta}$ and pro-IL-18 in THP-1 macrophages by the activation of p38 MAPK and NF-${\kappa}B$ through RAGE. HMGB1 likely plays an important role in the first step of the release of the IL-$1{\beta}$ and IL-18, preparing for other cytokines to induce excessive release of IL-$1{\beta}$ and IL-18 which promote inflammation and cancer progression.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.447-454
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• 2023

In the environment in which humans live, there are various antigens that invade the human body and interfere with humans leading a healthy life, so the immune system recognizes the antigen then removes them through a complex mechanism. Macrophages are widely distributed immune cells involved in the innate immune system, and produce various immune modulators such as inducible nitric oxide synthase-induced nitric oxide, cyclooxygenase-2 induced prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor-alpha. On the other hand, Protaetia brevitarsis seulensis larvae are a type of edible insect that have emerged as an alternative to the future food supply problem. The immuno-modulatory effect through the activation of murine macrophage RAW264.7 cell via mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B (NF-κB) signaling pathways has been reported. Based on this report, in this study, we confirmed how the expression of immune modulators induced by Protaetia brevitarsis seulensis larvae extracts in RAW264.7 cells was changed by treatment with pharmacological inhibitors of toll-like receptor 4 (TLR4), MAPKs and NF-κB signaling pathways. As a result, reduction of immune modulators was confirmed in the c-Jun N-terminal kinase (JNK) inhibitor treatment group and NF-κB inhibitor treatment group among the Protaetia brevitarsis seulensis larvae-treated RAW264.7 cell. Furthermore, in the TLR4 inhibitor-treated group, decreases in phosphorylation of JNK and NF-κB factors were confirmed in Protaetia brevitarsis seulensis larvae-treated RAW264.7 cell, as well as decreases in immune modulators. This results suggest that Protaetia brevitarsis seulensis larvae activates RAW264.7 cells by the engagement of TLR4-JNK/NF-κB signaling pathway.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.85-93
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• 2015

Objectives : Bilobalide (BIL) is a predominant sesquiterpene trilactone constituent that accounts for a partial portion of the standardized Ginkgonis Folium extract, which has been widely used to treat a variety of neurological disorders involving cerebral ischemia and neurodegeneration. In this study, it was tested whether BIL exhibits anti-inflammatory activities on inflammation response, or not. Methods : To elucidate the molecular mechanisms of BIL on pharmacological and biochemical actions in inflammation, we examined the effect of BIL on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation was focused on how BIL affect on inflammation-related mediators including various signals such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), interleukin-6(IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), mitogen-activated protein kinases(MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) in LPS-stimulated RAW 264.7 cells. Results : We found that BIL inhibited LPS-induced NO, $PGE_2$, IL-6 and $TNF-{\alpha}$ productions as well as the expressions of iNOS and COX-2. Furthermore, BIL suppressed the LPS-induced phosphorylation for MAPK activation. Conclusions : These results suggest that BIL has inhibitory effects on LPS-induced $PGE_2$, NO, IL-6 and $TNF-{\alpha}$ production, as well as the expressions of iNOS and COX-2 in the murine macrophage. It seems that these inhibitory effects occur by blocking the phosphorylation of MAPKs for activation. Then, BIL suppressed the activation of nuclear factor $NF-{\kappa}B$ in nucleus. These observations suggest that BIL has anti-inflammatory effect by inhibiting.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.117-117
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• 2004

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.133-134
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• 2001

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.150.1-150.1
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• 2000