• IMMUNE NETWORK
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• v.20 no.4
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.311-317
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• 2019

Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation ($IC_{50}$, ${\sim}1.42{\mu}M$). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-${\alpha}$ ($IC_{50}$, ${\sim}1.10{\mu}M$), and IL-6 ($IC_{50}$, ${\sim}1.24{\mu}M$). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, $PLC{\gamma}$, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.

• Journal of Microbiology and Biotechnology
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• v.25 no.6
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• pp.946-950
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• 2015

Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drugsensitive or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis activity against drug-sensitive strains (MIC, 3.125-6.25 µg/ml) as well as drugresistant strains (MIC, 6.25 to 12.5 µg/ml). In addition, tamoxifen profoundly decreased the number of intracellular TB in macrophages in a dose-dependent manner.

• Natural Product Sciences
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• v.13 no.2
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• pp.169-173
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• 2007

Luteolin is a major flavonoid of Lonicera japonica and has anti-inflammatory effect. The activation of proteinase-activated receptor (PAR)-2 and -4 by trypsin appears to play a role in inflammation, In the present study, we examined the inhibitory effects of luteolin on activation of trypsin-induced human leukemic mast cells (HMC-1). HMC-1 cells were stimulated with trypsin, PAR-2 and PAR-4 agonist, in the presence or absence of luteolin. The level of TNF-${\alpha}$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). The expression of tryptase and phosphorylated-extracellular signal-regulated kinase (ERK) were assessed by Westem blot analysis. Moreover, trypsin activity was measured by the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). TNF-${\alpha}$ secretion and Tryptase expression in trypsin-stimulated HMC-1 cells were markedly inhibited by pretreatment of luteolin. Furthermore, the pretreatment of luteolin resulted in the reduction of ERK phosphorylation and trypsin activity. These results suggest that luteolin might has the inhibitory effects on the PAR-2 and -4-dependent inflammation.

• Journal of Magnetics
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• v.18 no.3
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• pp.289-296
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• 2013

This work presents results of the study which concerns the influence of the rotating magnetic field (RMF) on the growth rate, cell metabolic activity and ability to form biofilms by E. coli and S. aureus. Liquid cultures of the bacteria were exposed to the RMF (RMF frequency f = 1-50 Hz, RMF magnetic induction B = 22-34 mT, time of exposure t = 60 min, temperature of incubation $37^{\circ}C$). The present study indicate the exposition to the RMF, as compared to the unexposed controls causing an increase in the growth dynamics, cell metabolic activities and percentage of biofilm-forming bacteria, in both S. aureus and E. coli cultures. It was also found that the stimulating effects of the RMF exposition enhanced with its increasing frequencies and magnetic inductions.

• IMMUNE NETWORK
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• v.13 no.1
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• pp.25-29
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• 2013

Ribavirin is an antiviral drug used in combination with pegylated interferon-${\alpha}$ (IFN-${\alpha}$) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on $CD4^+$ $CD4^+$ $CD25^+$ Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that ribavirin treatment did not modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the effect of ribavirin on Treg cells in the presence of IFN-${\alpha}$; however, the expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the presence of IFN-${\alpha}$. Next, we directly evaluated the effect of ribavirin on the suppressive activity of Treg cells in the standard Treg suppression assay, by co-culturing CFSE-labeled non-Treg $CD4^+$ T cells with purified Treg cells. We found that ribavirin did not attenuate the suppressive activity of Treg cells. Taken together, while ribavirin reversed Treg cell-mediated suppression of effector T cells in the previous study, we herein demonstrate that ribavirin does not impair the suppressive activity of Treg cells.

• Osong Public Health and Research Perspectives
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• v.9 no.6
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• pp.334-339
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• 2018

Objectives: Human rhinoviruses (HRVs) are the major cause of the common cold. Currently there is no registered, clinically effective, antiviral chemotherapeutic agent to treat diseases caused by HRVs. In this study, the antiviral activity of dexamethasone (DEX) against HRV1B was examined. Methods: The anti-HRV1B activity of DEX was assessed by sulforhodamine B assay in HeLa cells, and by RT-PCR in the lungs of HRV1B-infected mice. Histological evaluation of HRV1B-infected lungs was performed and a histological score was given. Anti-HRV1B activity of DEX via the glucocorticoid receptor (GCR)-dependent autophagy activation was assessed by blocking with chloroquine diphosphate salt or bafilomycin A1 treatment. Results: In HRV1B-infected HeLa cells, treatment with DEX in a dose-dependent manner, resulted in a cell viability of > 70% indicating that HRV1B viral replication was reduced by DEX treatment. HRV1B infected mice treated with DEX, had evidence of reduced inflammation and a moderate histological score. DEX treatment showed antiviral activity against HRV1B via GCR-dependent autophagy activation. Conclusion: This study demonstrated that DEX treatment showed anti-HRV1B activity via GCR-dependent autophagy activation in HeLa cells and HRV1B infected mice. Further investigation assessing the development of topical formulations may enable the development of improved DEX effectiveness.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.141-147
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• 2013

Hypoxia has been shown to promote inflammation, including the release of proinflammatory cytokines, but it is poorly investigated how hypoxia directly affects inflammasome signaling pathways. To explore whether hypoxic stress modulates inflammasome activity, we examined the effect of cobalt chloride ($CoCl_2$)-induced hypoxia on caspase-1 activation in primary mixed glial cultures of the neonatal mouse brain. Unexpectedly, hypoxia induced by oxygen-glucose deprivation or $CoCl_2$ treatment failed to activate caspase-1 in microglial BV-2 cells and primary mixed glial cultures. Of particular interest, $CoCl_2$-induced hypoxic condition considerably inhibited NLRP3-dependent caspase-1 activation in mixed glial cells, but not in bone marrow-derived macrophages. $CoCl_2$-mediated inhibition of NLRP3 inflammasome activity was also observed in the isolated brain microglial cells, but $CoCl_2$ did not affect poly dA:dT-triggered AIM2 inflammasome activity in mixed glial cells. Our results collectively demonstrate that $CoCl_2$-induced hypoxia may negatively regulate NLRP3 inflammasome signaling in brain glial cells, but its physiological significance remains to be determined.

• Journal of Integrative Natural Science
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• v.17 no.2
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• pp.59-65
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• 2024

Dendritic cells play a very important role in the immune response as antigen-presenting cells that are critical for initiating both innate and acquired immunity. They recognize, process and present foreign antigens to other key immune cells to trigger and regulate the immune response. The ability to activate these dendritic cells can be used as a treatment for various immune diseases. Maqui berry has been reported to have anticancer, antibacterial and anti-inflammatory properties. However, its effect on the activity of dendritic cells has not been studied. In this study, we investigated the efficacy of maqui berry extract in modulating dendritic cell activity. Treatment of dendritic cells with maqui berry extract induced the costimulatory molecules CD80, CD86, and MHC class I and II in a concentration-dependent manner. Furthermore, the antigen-presenting capacity of dendritic cells was inhibited, which confirms their ability to present antigens, and the production of Interleukin (IL)-12, which is important for dendritic cell activity, was increased. These results indicated that Maqui berry extract activates dendritic cells maturation by inducing the production of co-stimulatory molecules and IL-12. These results suggest that maqui berry extract may act as an effective adjuvant to enhance dendritic cell-based immune responses.

• IMMUNE NETWORK
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• v.5 no.3
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• pp.172-178
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• 2005

Background: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. However, it is known that the induction of immune response to CEA is very difficult because CEA is a self-antigen expressed in fetal cells and weakly expressed in normal colorectal epithelial cells. To enhance anti-tumor immunity specific for CEA, recombinant CEA protein was modified using listeriolysin O (LLO) for endosomal lysis and trans activator of transcription (Tat) domain for transducing extracellular proteins into cytoplasm. Methods: After immunization using dendritic cells pulsed with Tat-CEA, both Tat-CEA and LLO, and both Tat-CEA and Tat-LLO, antibody titer to CEA and LLO, cytotoxic T lymphocyte activity and the frequency of IFN-${\gamma}$ producing T lymphocytes were measured. Results: Immunization using DC pulsed with both Tat-CEA and Tat-LLO protein showed the increasement of production of CEA-specific antibody in serum, cytotoxic T lymphocyte activity, the frequency of IFN-${\gamma}$ secreting T cells, compared with DC pulsed with both Tat-CEA and LLO. Furthermore the ratio of CD8+T cell to $CD4^+$ cell among CEA-specific T cells was increased in group pulsed with both Tat-CEA and Tat-LLO. Conclusion: These results suggested that DC vaccine using Tat-LLO could be used for the development of effective immunotherapy for the treatment of tumor.