• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.263-268
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• 2015

5-Lipoxygenase (5-LO) plays a pivotal role in the progression of atherosclerosis. Therefore, this study investigated the molecular mechanisms involved in 5-LO expression on monocytes induced by LPS. Stimulation of THP-1 monocytes with LPS ($0{\sim}3{\mu}g/ml$) increased 5-LO promoter activity and 5-LO protein expression in a concentration-dependent manner. LPS-induced 5-LO expression was blocked by pharmacological inhibition of the Akt pathway, but not by inhibitors of MAPK pathways including the ERK, JNK, and p38 MAPK pathways. In line with these results, LPS increased the phosphorylation of Akt, suggesting a role for the Akt pathway in LPS-induced 5-LO expression. In a promoter activity assay conducted to identify transcription factors, both Sp1 and NF-${\kappa}B$ were found to play central roles in 5-LO expression in LPS-treated monocytes. The LPS-enhanced activities of Sp1 and NF-${\kappa}B$ were attenuated by an Akt inhibitor. Moreover, the LPS-enhanced phosphorylation of Akt was significantly attenuated in cells pretreated with an anti-TLR4 antibody. Taken together, 5-LO expression in LPS-stimulated monocytes is regulated at the transcriptional level via TLR4/Akt-mediated activations of Sp1 and NF-${\kappa}B$ pathways in monocytes.

• 대한의생명과학회지
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• 제26권2호
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• pp.85-92
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• 2020

Various beneficial effects of sweet persimmon (Diospyros kaki T.) including anti-oxidation, anti-bacteria and viruses, anti-allergy were widely reported previously. However, the anti-inflammatory effect and its molecular mechanisms are not clear. In this study, the anti-inflammatory effect of the extracts of flower bud and fruit of sweet persimmon was investigated in LPS-treated RAW264.7 cells. Both extracts of flower bud and fruit showed strong inhibitory effect on the LPS-induced NF-κB activation. IκBα, the inhibitor of NF-κB, was increased and the expressions of NF-κB target genes, COX-2 and iNOS, were suppressed by the treatment with the extracts of flower bud and fruit. The expressions of pro-inflammatory cytokines, IL-1β, IL-6, TNF-α were also suppressed by the extracts. In addition, the LPS-induced wnt/β-catenin pathway and its related gene expressions including cyclin D1, wnt 3a, wnt 5a were suppressed by the extracts. The extracts also showed anti-oxidant activity and suppressive effect on the LPS-induced apoptosis of RAW264.7 cells. These results suggest that the flower bud and fruit of sweet persimmon display strong anti-inflammatory effect through inhibiting the pro-inflammatory signaling pathways in the cells.

• IMMUNE NETWORK
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• 제13권2호
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• pp.55-62
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• 2013

Swiprosin-1 exhibits the highest expression in $CD8^+$ T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that $PKC-{\theta}$ is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with $NF-{\kappa}B$ inhibitors but not by NF-AT inhibitor, suggesting that the $NF-{\kappa}B$ pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a $PKC-{\theta}$-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.92-100
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• 2019

Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.

• Journal of Ginseng Research
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• 제48권4호
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• pp.384-394
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• 2024

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

• BMB Reports
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• 제46권11호
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• pp.533-538
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• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• BMB Reports
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• 제53권4호
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• pp.223-228
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• 2020

Dysregulation of histone deacetylase 6 (HDAC6) can lead to the pathologic states and result in the development of various diseases including cancers and inflammatory diseases. The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-κB and AP-1 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. LPS-induced expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. Taken together, these data provide evidence that miR-22 can downregulate LPS-induced expression of pro-inflammatory cytokines via suppression of NF-κB and AP-1 axis by targeting HDAC6 in macrophages.

• 대한의생명과학회지
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• 제18권3호
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• pp.307-309
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• 2012

(S)-(+)-3(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo3,4-dihydro-2H,8H-pyrano[3,2-g]Chromen-3-yl-ester (Compound 6, C6) is synthesized from (S)-(+)-decursin and attenuates the pathophysiologic progression of asthma in a ovalbumin-induced asthmatic mouse model. In the present study, we examined the effect of C6 on spontaneous apoptosis of eosinophils and neutrophils of normal and asthmatic subjects. C6 increased the apoptosis of asthmatic eosinophils in a dose-dependent manner, but it inhibited neutrophil apoptosis. C6 has no effect on apoptosis of normal eosinophils and neutrophils. LY294002, an inhibitor of PI3K, rottlerin, an inhibitor of $PKC{\delta}$, Ro-31-8425, an inhibitor of classical PKC inhibitor, PD98059, an inhibitor of MEK, and BAY 11-7085, an inhibitor of NF-${\kappa}B$, blocked the inhibitory effect on apoptosis of asthmatic neutrophils due to C6. These results indicate that C6 may be valuable as a therapeutic agent for the treatment of asthma.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.107-107
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• 2022

Scrophularia koraiensis Nakai is widely used to remedy fever, edema, and neuritis. S. koraiensis has harpagoside and angoroside C, these compounds have been reported to alleviate inflammation, rheumatic diseases, and analgesic stimulation. We evaluated the anti-inflammatory effects of the ethanol extract of S. koraiensis (SKE) in lipopolysaccharides (LPS)-induced macrophages. At cellular levels, SKE decreased the production of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), and cytokines (IL-1b, TNF-a, and IL-6) under the LPS stimulation. SKE inhibited the phosphorylation of nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor (IκB-α). In addition, SKE suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in the mitogen-activated protein kinase (MAPK) pathway. In conclusion, SKE could be considered a potential resource for attenuating inflammation response and it may be utilized in the material for cosmetics, food additives, and tea.

• 대한한방부인과학회지
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• 제32권3호
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• pp.32-56
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• 2019

Objectives: The purpose of this study was to investigate the in vitro anti-inflammatory, anti-pruritic and antimicrobial effects of the three herbal prescription (EST, SCT, WDT), which has been traditionally used for treating leukorrhea induced by various infections in the female genital tract. Methods: In this experiment, the anti-inflammatory effects were evaluated by Nitric oxide (NO), $Interlukine-1{\beta}$ ($IL-1{\beta}$), Interlukine-2 (IL-2), Interlukine-6 (IL-6), Tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), Prostaglandin $E_2$ ($PGE_2$), Leukotriene $B_4$ ($LTB_4$) production amount and Inducible nitric oxide synthase (iNOS), Nuclear factor kappa B ($NF-{\kappa}B$), Cyclooxygenase-2 (COX-2) gene expression levels in RAW264.7 cells. And the anti-pruritic effects were evaluated by Histamine, Acetylcholine (ACh), Acetylcholinesterase (AChE), Substance P production amount in Mast cell/9 (MC/9) and Pheochromocytoma 12 (PC12) cells. The anti-microbial effect was measured by inhibition zone diameter on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. Results: As a result of measuring anti-inflammatory efficacy, $IL-1{\beta}$, IL-2, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$ production amounts were significantly reduced in the EST, SCT, WDT extraction groups compared with the control group, and significantly decreased the amount of $NF-{\kappa}B$, iNOS, and COX-2 gene expression and the amount of Phospho-Inhibitor kappa B alpha ($p-I{\kappa}B-{\alpha}$)/Inhibitor kappa B alpha ($I{\kappa}B-{\alpha}$) and $NF-{\kappa}B$ p65 protein expression. In addition, As a result of measuring the anti-pruritic effect, the amounts of histamine, ACh and Substance P were significantly decreased, and AChE production was slightly decreased, but it's significance did not appear. Finally the anti-microbial effects of EST, SCT, WDT extraction groups against Pseudomonas aeruginosa, Candida albicans and Aspergillus niger was inhibited, however the growth of Escherichia coli and Staphylococcus aureus was not inhibited. Conclusions: These data suggest that EST, SCT, WDT can be used to treat patients with leukorrhea.