• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.319-325
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• 2002

The induction of interleukin-6 (IL-6) using combined proinflammatory agents $(LPS/IFN-{\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ was studied in relation to p38 mitogen-activated protein kinase (MAPK) and $NF-{\kappa}B$ transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents $(LPS/IFN-[\gamma}\;or\;TNF-{\alpha}/IFN-{\gamma})$ had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, $IFN-{\gamma}$ enhancement of $TNF-{\alpha}-induced\;NF-{\kappa}B$ binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on $TNF-{\alpha}/IFN-{\gamma}\;or\;LPS/IFN-{\gamma}-induced\;NF-{\kappa}B$ activation. This study strongly suggests that these pathways about $TNF-{\alpha}/IFN-{\gamma}$ or $LPS/IFN-{\gamma}-activated$ IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.930-936
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.916-920
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• 2007

Flowers of Magnolia denudata has been reported to possess a variety of pharmacological activities. In this study, we investigated the anti-inflammatory effects and mechanism of the water extract of Flowers of Magnolia denudata(MD) in lipopolysacchride (LPS)-mediated inflammatory mediators in murine peritoneal macrophages. MD itself does not have any toxic effects in murine peritoneal macrophages. MD inhibits LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, IL-6 and IL-12 production in murine peritoneal macrophages. Furthermore, we have found that MD inhibited LPS-induced $NF-{\kappa}B$ but not c-Jun N-terminal kinase (JNK), p38 and extracellular signal-ragulated kinase (ERK) activation. These results suggested that MD inhibit LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-12 via suppression of the $NF-{\kappa}B$ activation.

• Journal of Acupuncture Research
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• v.39 no.4
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• pp.304-309
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• 2022

Background: This study was conducted to determine the anti-inflammatory effect of astaxanthin, on atopic dermatitis. Methods: Changes in mouse body weight, lymph node weight, and the degree of improvement in symptoms were measured to determine the inflammatory response. Real-time reverse transcription-polymerase chain reaction tests were performed to determine the degree of expression of inflammation-related cytokines (IL-31 and IL-33 and chemokines such as CCL17 and CCL22), and western blot analysis was performed to evaluate the expression of inflammation-related factors (iNOS, COX-2, and NF-kB signaling molecules p-IkBα, p50, p-65 and pSTAT3). Results: The degree of symptoms significantly improved in the PA+AX group. Lymph node weight in the PA+AX group was lower than the PA group. Inflammatory cytokines (IL-31, IL-33, and inflammatory chemokines such as CCL17 and CCL22) were significantly reduced in the PA+AX group compared with the PA group. The expression of inflammatory genes (iNOS, COX-2, NF-kB and signaling molecules (p-IkBα, p50, p65, and p-STAT 3) was lower in the PA+AX group compared with the PA group. Conclusion: Astaxanthin may modulate the inflammatory response in a mouse model of atopic dermatitis and has an anti-inflammatory effect.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.127-134
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• 2018

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB ($NF-{\kappa}B$) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

• BMB Reports
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• v.38 no.3
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• pp.281-289
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• 2005

Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors, TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and biological roles. In the present study, TNFR2 and TNFR1 signal transduction mechanisms involved in activation of $NF{\kappa}B$ and CMV promoter-enhancer were compared with respect to their susceptibility towards inhibitors of intracellular signaling. For this, we used SW480 cells, where we have shown that TNF-signaling can occur independently through each of the two receptors. The TNFR1 response was inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA), and by sodium salicylate, while TNFR2-mediated activation of $NF{\kappa}B$ and CMV promoter-enhancer was resistant to these compounds. The signaling mechanisms known to be affected by these inhibitors include phospholipases as well as redox- and pH-sensitive intracellular components. Our results imply that TNFR2 signaling involved in $NF{\kappa}B$ activation proceeds independently of these inhibitor-sensitive signaling components, indicating distinct signaling pathways not shared with TNFR1.

• Korean Journal of Food Science and Technology
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• v.44 no.6
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• pp.759-762
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• 2012

Egg allergies have been reported as one of the most prevalent food hypersensitivities in the pediatric population. One of the major egg allergens is ovalbumin (OVA), which is the major protein in the egg whites. Phenethyl isothiocyanate (PEIC) from cruciferous vegetables has an effect on anti-inflammatory therapy. In the present report, we show that PEIC inhibits the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation induced by OVA. PEIC also inhibits the OVA-induced inducible nitric oxide synthase (iNOS) expression and nitrite production. However, PEIC did not suppress the cyclooxygenase-2 (COX-2) expression induced by OVA. These results suggest that PEIC has the specific mechanism for anti-inflammatory responses and efficient anti-allergic activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.533-539
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• 2011

Sulfuretin is one of the main flavonoids produced by Rhusverniciflua. Sulfuretin has been shown to exhibit many pharmacological activities including anti-oxidant, anti-obesity, anti-inflammatory and anti-mutagenic activities. However, the anti-skin photoaging effects of sulfuretin has not yet been reported. In the present study, we investigated the inhibitory effect of sulfuretin on the expression levels of MMP-1 and -3 in the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed sulfuretin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB-induced MAPK/NF-${\kappa}B$/p50 activation and MMP expression were completely blocked by pretreatment of sulfuretin. Taken together, sulfuretin could prevent UVB-induced MMP expressions through inhibition of MAPK/NF-${\kappa}B$/p50 activation.

• Molecules and Cells
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• v.27 no.2
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• pp.211-215
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• 2009

Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B ($NF-{\kappa}B$). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of $NF-{\kappa}B$ activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.

• Molecules and Cells
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• v.39 no.5
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• pp.403-409
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• 2016

NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with $IKK{\beta}$ and regulating its activity. In the present study, we tried to define the role of the N-terminal 25 amino acids of NME1L in $NF-{\kappa}B$ activation signaling. Unfortunately, the sequence itself did not interact with $IKK{\beta}$, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, $IKK{\beta}$ interaction and regulation of $NF-{\kappa}B$ signaling. The inhibitory effect of the fragment on cancer cell migration and $NF-{\kappa}B$-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and $IKK{\beta}$ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and $IKK{\beta}$-related anti-cancer drug design.