• Korean Journal of Poultry Science
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• v.44 no.3
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• pp.199-209
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• 2017

Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.3
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• pp.40-59
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• 2020

Objectives: The purpose of this study was to investigate the anti-inflammatory effects of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos in vitro, which has been frequently used in inflammatory diseases. Methods: In this experiment, the anti-inflammatory effects of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos were evaluated by checking the following substances of LPS-activated Raw264.7 cell: Prostaglandin E₂ (PGE₂), Nitric oxide (NO), Cyclooxygenase-2 (COX-2), inducible Nitric oxide synthase (iNOS), Interlukine-1β (IL-1β), Interlukine-6 (IL-6), Tumor necrosis factor-α (TNF-α), mitogen-activated protein kinase (MAPK), Inhibitor of kappa B-α (IκBα), Nuclear factor kappa B (NF-κB). And additionally measured reactive oxygen species (ROS) and free radicals to check the antioxidant effect of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos which affect inflammatory responses. Results: As a result of measuring anti-inflammatory efficacy, PGE2, NO, IL-1β, IL-6, TNF-α production amounts were reduced in the ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos groups compared with the control group, and decreased the amount of COX-2 mRNA, iNOS mRNA gene expression. Expression of MAPK (ERK, JNK, p38) pathway was decreased. Expression of IκBα was increased and NF-κB was decreased. It is demonstrated that ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos, by reducing NF-κB, regulate the expression of the inflammatory genes and reduce the inflammatory mediators. Ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos also decreased ROS production and free radicals, which shown to have antioxidant efficacy and influence anti-inflammatory effects. Conclusions: These data suggest that ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos can be used to treat various inflammatory diseases.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.297-304
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• 2005

Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ($\cdot$NO) as well as peroxynitrite (ONOO$\kappa$) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC$_{50}$ values of 13.9, 20.1 and 26.8 $\mu$M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF-$\kappa$B and C/EBP$\beta$. Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

• BMB Reports
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• v.43 no.10
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• pp.656-663
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• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.

• Journal of the Korean Magnetic Resonance Society
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• v.14 no.2
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• pp.127-133
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• 2010

Redox-dependent conformational change of human 8-kDa Dynein light chain (LC8) plays important role in regulating NF-${\kappa}B$ signaling pathway. In this study we characterized the structural states of the oxidized and reduced forms of LC8 by using NMR spectroscopy. The $^1H-^{15}N$ 2D HSQC spectra of oxidized LC8 indicated that no significant change in tertiary structure of LC8 occurred upon oxidation. The chemical shift perturbations of LC8 upon oxidation suggest a redox-dependent quaternary structural change.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.5
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• pp.402-407
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• 2006

Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.31-32
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• 2001

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.155-159
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• 2017

Cudrania tricuspidata Bureau (Moraceae) is a traditional oriental medicine that has been widely used as anti-oxidant, anti-inflammatory and immunomodulatory in Korea. This study was performed that the 70% ethanol extract of the roots of C. tricuspidata (CTE) suppressed receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis, actin ring formation in RAW 264.7 cell lines. CTE significantly inhibited the JNK/mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells. Also, CTE inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1. Consequently, CTE suppresses osteoclast differentiation by inhibiting RANKL induced MAPK signaling pathways and disrupts the actin rings in mature osteoclasts. Thus, CTE can be used for the development of osteoporosis treatment drug with a natural material.

• The Journal of Korean Obstetrics and Gynecology
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• v.24 no.1
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• pp.15-26
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• 2011

Objectives: The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Cicadidae Periostracum(CP) on the RAW 264.7 cells. Method: We examined the cytokine productions including nitric oxide(NO), interleukin(IL)-1b, IL-6 and tumor necrosis factor-a(TNF-a) in lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms such as mitogen -activated protein kinases(MAPKs) and nuclear factor kappa BNF-kB) using Western blot. Results: CP inhibited LPS-induced production of NO, IL-1b and TNF-a but not of IL-6 in RAW 264.7 cells. CP respectively inhibited the activation of MAPKs such as extracelluar signal-regulated kinase(ERK 1/2), c-Jun $NH_2$-terminal kinase(JNK), p38 and NF-kB in the LPS-stimulated RAW 264.7 cells. Also oral administration of CP inhibited CLP - induced endotoxin shock. Conclusion: our results showed that CP down-regulated LPS-induced NO, IL-1b and TNF-a productions mainly through ERK, JNK, p38 MAPK and NF-kB pathway, which suggest the anti-inflammatory effects of CP.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.216-222
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• 2011

Background: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages. Methods: We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway. Results: Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-${\alpha}$ mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-${\kappa}B$ ($IkB{\alpha}$). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-${\alpha}$, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-${\alpha}$ production. Conclusion: Our results suggest that TATCD137Lct is an effective activator for the CD137L reverse signaling pathway.