• Journal of Pharmacopuncture
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• v.15 no.1
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• pp.29-33
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• 2012

Objectives: Much evidence exists that herbs have effective immunomodulatory activities. Chrysanthemi Flos (CF) is effective in clearing heat, reducing inflammation, dropping blood pressure and treating headache and is used as a pharmaceutical raw material for an immune enhancer. The purpose of this study was to investigate the modulatory effect of Chrysanthemi Flos pharmacopuncture on nitric-oxide (NO) production in activating macrophages. Methods: After a murine macrophage cell line, RAW 264.7, was cultured in the presence of lipopolysaccharide (LPS), immune-modulating abilities of CF were evaluated by using NO, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-${\alpha}$) production and phagocytic activity of macrophages. Results: CF enhanced the activities of macrophages by increasing the phagocytic activity and decreasing NO production. Especially, both LPS and CF, 200 ${\mu}g/ml$, treatment could significantly reduce the NO production, but did not change the production of IL-6 and TNF-${\alpha}$. Conclusion: The results of this study indicate that CF may be of immunomodulatory value, especially for adverse diseases due to increased NO production. It may have potential for use as immunoenhancing pharmacopuncture.

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.531-534
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• 2000

Nitric oxide (NO), products of activated macrophages, have a great impact on the regulation of cytokine production. The role of NO in non-specific host cells is commonly accepted. On the contrary, its role as an immuno-regulatory molecule is still controversial. In this study, we have investigated the effect of NO on the production of cytokines from murine splenocytes and macrophages. S-nitroso-L-glutathione inhibited the release of both interferone-$\gamma$ and interleukin-2 produced by Th1 cells and tumor necrosis factor-$\alpha$ and interleukin-1$\beta$ produced by macrophages, but did not affect the release of interleukin-4 and interleukin-10 produced by Th2 cells. These results suggest that NO exerts a down-regulatory effect on the secretion of cytokines from Th1 cells and macrophages which are implicated in immune response. Thus, NO may have an important role as an immune-modulatory as well as effector molecule in the immune system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.1079-1083
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• 2015

Activating macrophage cells play an important role in the host immune defense system. In this paper, immuno-modulatory activities of polysaccharides separated from Jubak (JPS) in macrophage cells were investigated. Immuno-modulatory activities were estimated based on cell proliferation, nitric oxide (NO) and cytokine production, degree of mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-${\kappa}B$ phosphorylation in RAW264.7 macrophage cells. JPS (62.5 to $250{\mu}g/mL$) did not induce a cytotoxic event. Additionally, NO and proinflammatory cytokines (tumor necrosis factor-${\alpha}$ and interleukin-6) production significantly increased in a dose-dependent manner. Similarly, phosphorylation of MAPKs and NF-${\kappa}B$ increased upon JPS treatment. Therefore, our results suggest that polysaccharides separated from Jubak can induce macrophage activation through MAPK and NF-${\kappa}B$ signaling and induction of Th1 polarization.

• Korean Journal of Medicinal Crop Science
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• v.16 no.1
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• pp.9-15
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• 2008

Immune-potentiation of Chicorium endivia L. were investigated on follows extracts associated with ultrasonification process at 60 kHz and showed the highest promotion of human B and T cell growth, about $10{\sim}20%$ compared to the control. The secretion of TNF-${\alpha}$ and IL-6 was also enhanced by the addition $(0.5mg/m{\ell})$ of the extracts. NK cell activation was Improved up to 1.37 times higher than the control, through adding extracts. It was also found that extracts from C. endivia L. could yield higher nitric oxide production from macrophage than Lipopolysaccaharides (LPS). It can be concluded that, in general, the extracts treated with ultrasonification has higher immune activity than others, possibly by higher yielding immune-modulatory activity than conventional extraction process. The optimum condition for the extraction of C. endivia L. is ethanol extraction at $60{\sim}100^{\circ}C$ associated with ultrasonification.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1285-1288
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• 2008

The purpose of this study was to characterize and investigate the immune activity of CpG oligodeoxynucleotides (ODNs) from Bifidobacterium longum. Bacterial CpG motifs have attracted considerable interests because of their immunomodulatory activities. Genomic DNA from B. longum was prepared and amplified for 4 different 180-188-mer double-stranded ODNs (BLODN1-BLODN4). When immune cells (RAW 264.7 murine macrophages and JAWS II dendritic cells) with these ODNs were treated, BLODN4 induced the highest immune activity. To assess the effectiveness of the CpG sequences within BLODN4, single-stranded 40-mer ODNs containing CpG sequences (sBLODN4-1, sBLODN4-2) were synthesized. sBLODN4-1 induced higher level of cytokines such as interleukin (IL)-12p40 and tumor necrosis factor (TNF)-$\alpha$ by macrophage and IL-6 and TNF-$\alpha$ by dendritic cells than did sBLODN4-2. The results suggest that CpG ODNs-enriched components of B. longum might be useful as an immunomodulatory functional food ingredient.

• 한국약용작물학회:학술대회논문집
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• 2007.11a
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• pp.289.2-289.2
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• 2007

• YAKHAK HOEJI
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• v.59 no.1
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• pp.1-5
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• 2015

Cordyceps militaris has shown to have various pharmacological activities including an immune-modulatory effect. Previously, we reported that anti-influenza effect of C. militaris in DBA/2 mice was mediated by increased IL-12 and the activation of NK cells. In this study, we investigated the effect of C. militaris on adaptive immune responses using DBA2 mice immunized with influenza vaccine. To determine the effect of C. militaris on antigen presentation capability, we treated RAW 264.7 cells with various concentrations of ethanol extract of C. militaris, which showed a significant upregulation of CD86 (B7.2), CD284 (TLR4), CD40, H-2k (MHC I) and I-Ad (MHC II). To examine the direct effect of C. militaris on adaptive immune responses, we immunized DBA2 mice with influenza vaccine in presence or absence of C. militaris. After 2 or 4 weeks, influenza-specific T cell proliferation, HAI titers and IFN-${\gamma}$ production were measured in plasma or PBMCs isolated from animals. Influenza-specific T cell proliferation and HAI titers were not considerably increased in immunized mice in presence of C. militaris. However, the production of IFN-${\gamma}$ was much greater in immunized mice with C. militaris as adjuvant than only immunized mice.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.134-141
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• 2010

It is well known that the numbers and functions of immune-associated cells are increased by saponins and polysaccharides in ginseng. In this study, the mixture of polysaccharide and saponin (MPS) from Panax ginseng is applied to LPS- activated RAW 264.7 cells. The production of NO and the gene expression of IL-6 and TNF-$\alpha$ are decreased in LPSactivated RAW 264.7 cells and the expression of arginase II and PD-1L genes is decreased in LPS-untreated macrophages. Therefore, the mixture of saponin and polysaccharide from Panax ginseng could be used in order to regulate immune responses.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• Journal of Microbiology
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• v.44 no.2
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• pp.217-225
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• 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with RBP-Jk that is a downstream transcription factor of the Notch signaling pathway that is important in development and cell fate determination. This suggests that KSHV RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. Here, I demonstrated that unlike other B lymphoma cells, KSHV -infected primary effusion lymphoma BCBL1 cells displayed the constitutive activation of ligand-mediated Notch signal transduction, evidenced by the Jagged ligand expression and the complete proteolytic process of Notch receptor I. In order to investigate the effect of Notch signal transduction on KSHV gene expression, human Notch intracellular (hNIC) domain that constitutively activates RBP-Jk transcription factor activity was expressed in BCBL1 cells, TRExBCBL1-hNIC, in a tetracycline inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes including KS immune modulatory gene resulting in downregulation of MHC I and CD54 surface expression. Finally, the genetic analysis of KSHV genome demonstrated that the hNIC-mediated expression of KS during viral latency consequently conferred the downregulation of MHC I and CD54 surface expression. These results indicate that cellular. Notch signal transduction provides a novel expression profiling of KSHV immune deregulatory gene that consequently confers the escape of host immune surveillance during viral latency.