• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• Genomics & Informatics
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• v.17 no.1
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• pp.8.1-8.10
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• 2019

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

• Journal of Acupuncture Research
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• v.33 no.1
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• pp.47-56
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• 2016

Objectives : This study examined the effects of Bee venom on apoptosis in NCI-H157 human lung cancer cells and for promoting the apoptosis effects of Natural killer cell. Methods : Bee venom and Natural killer-92 cells were cultured either separately from or together with NCI-H157 cells for 24 hours. To figure out whether Bee venom enhances the cytotoxic effect of Natural Killer-92 cells, a cell viability assay was conducted. To observe the changes in Death receptors, apoptotic regulatory proteins and Nuclear $Factor-{\kappa}B$, western blot analysis was conducted. To observe the effect of Bee venom through an extrinsic mechanism, a transfection assay was conducted. Results : 1. Natural killer-92 cells and Bee venom significantly inhibited the growth of NCI-H157 cells and co-culture had more inhibitory effect than the separate culture. 2. Expressions of Fas, DR3, DR6, Bax, caspase-3, caspase-8, cleaved caspase-3, cleaved caspase-8 were increased, and expressions of Bcl-2 and cIAP were decreased. More efficacy was observed in co-culture than in separate culture. 3. Nuclear $Factor-{\kappa}B$ activation was clearly decreased. And co-culture showed much less activation than separate culture. 4. As a result of treatment for DR-siRNA, the reduced cell viability of NCI-H157 cells and the activity of Nuclear $Factor-{\kappa}B$ were increased. With this, it can be seen that Bee venom and Natural killer-92 cells have an effect on the cancer cells through the extrinsic mechanism. Conclusion : Bee venom is effective in inhibiting the growth of human lung cancer cells. Furthermore Bee venom effectively enhances the functions of Natural killer cells.

• Molecules and Cells
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• v.38 no.7
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• pp.638-642
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• 2015

Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than $10{\mu}M$ inhibited 143B proliferation, while $5{\mu}M$ quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, $5{\mu}M$ quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.

• IMMUNE NETWORK
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• v.15 no.1
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• pp.1-8
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• 2015

Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.821-828
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• 2008

Onchungeum, a herbal formula, which has been used for treatment of anemia due to bleeding, discharging blood and skin disease. In the present study, it was examined the effects of extract of Onchungeum (OCE) on the growth of human hepatocarcinoma cell lines Hep3B (p53 null type) and HepG2 (p53 wild type) in order to investigate the anti-proliferative mechanism by OCE. Treatment of Hep3B and HepG2 cells to OCE resulted in the growth inhibition in a dose-dependent manner, however Hep3B cell line exhibited a relatively strong anti-proliferative activity to OEC. Flow cytometric analysis revealed that OCE treatment in Hep3B cells caused G1 phase arrest of the cell cycle, which was associated with various morphological changes in a dose-dependent fashion. RT-PCR and immunoblotting data revealed that treatment of OCE caused the down-regulation of cyclin D1 expression, however the levels of cyclin E expression were not changed by OCE. The G1 arrest of the cell cycle was also associated with the induction of Cdk inhibitor p27 by OCE. Because the p53 gene is null in Hep3B cells, it is most likely that the induction of p21 is mediated through a p53-independent pathway. Moreover, p27 detected in anti-Cdk4 and anti-Cdk2 immunoprecipitates from the OCE-treated cells, suggesting that OCE-induced p27 protein blocks Cdk kinase activities by directing binding to the cyclin/Cdk complexes. Furthermore, OCE treatment potently suppresses the phosphorylation of retinoblastoma proteins and the levels of the transcription factor E2F-1 expression. Taken together, these results indicated that the growth inhibitory effect of OCE in Hep3B hepatoma cells was associated with the induction of G1 arrest of the cell cycle through regulation of several major growth regulatory gene products.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.200-208
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• 2011

Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.659-665
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• 2020

Adenophorae Radix (AR) has been used as a traditional medicine for various diseases. However, the regulatory mechanisms of AR in allergic inflammation are not yet understood. The present study was conducted to investigate the effect and mechanisms of AR on the mast cell-mediated allergic response. To determine the pharmacological mechanisms of AR in allergic inflammation, we evaluated the effects of AR on the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8 as well as the activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). Our results demonstrated that AR effectively attenuated the PMACI-induced production of TNF-α, IL-6, IL-1β and IL-8 in stimulated HMC-1. Additionally, we showed that the inhibitory effect of AR on inflammatory cytokines in PMACI-stimulated HMC-1 cells involved the suppression of the activation NF-kB/caspase-1 in PMACI-stimulated HMC-1. Collectively, these findings provide experimental evidence that AR may be a useful candidate for the treatment of allergic inflammation.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.93-99
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• 2022

Lysosome organelle extract (LOE) was derived from egg whites. The lysosome is an intracellular organelle that contains several hydrolysis enzymes. Previous studies have reported that LOE performs important functions, such as melanin de-colorization and anti-melanin production in B16F10 melanoma cells. However, its principal molecular and cellular mechanisms have not been elucidated till date. In non-cytotoxic conditions, LOE significantly inhibited α-MSH induced melanin synthesis of murine B16F10 cells. The anti-melanogenic activity of LOE was mediated by suppressing the mRNA expression of tyrosinase enzyme, tyrosinase related protein-1/2 (TRP-1/2), and microphthalmia-associated transcription factor (MITF) genes. By performing western blot analysis, we found that LOE significantly attenuated melanogenesis. In this case, LOE helped in increasing extracellular receptor kinase (ERK) phosphorylation in α-MSH induced B16F10 cells. Furthermore, MITF is found to be a key regulatory transcription factor in melanin synthesis; it was down-regulated by LOE through ERK phosphorylation. In this experiment, PD98059 (MEK inhibitor) was used to check whether LOE directly regulated the activity of ERK. Although LOE exerted inhibitory effect on melanin synthesis, we could not observe this effect in PD98059-treated α-MSH induced B16F10. These results strongly indicate that LOE is related to ERK activation and MITF degradation in anti-skin pigmentation. Hence, LOE should be utilized as a whitening agent of skin in the near future.

• Biomedical Science Letters
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• v.29 no.2
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• pp.58-65
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• 2023

Pu-erh tea, a popular and traditional Chinese tea, possesses various health-promoting effects, including inhibiting tumor cell progression and preventing type II diabetes and neurodegenerative disorders. However, the precise anti-inflammatory mechanisms are not well understood. In present study, we elucidated the anti-inflammatory mechanism of Pu-erh tea in lipopolysaccharide (LPS)-activated RAW264.7 cells. We explored the effects of Pu-erh tea on the levels of inflammatory-related genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin E₂ (PGE₂) in LPS-activated RAW264.7 cells. Moreover, we investigated its regulatory effects on nuclear factor-kappa B (NF)-κB and hypoxia-inducible-factor (HIF)-1α activation. The findings of this study demonstrated that Pu-erh tea inhibited the LPS-increased inflammatory cytokines and PGE₂ release, as well as COX-2 and iNOS expression. Moreover, we confirmed that the anti-inflammatory mechanism of Pu-erh tea occurs via the inhibition of NF-κB and HIF-1α activation. Conclusively, these findings provide experimental evidence that Pu-erh tea may be useful candidate in the treatment of inflammatory-related diseases.