• 대한한의학회지
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• 제17권2호
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.

• BMB Reports
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• 제39권6호
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• pp.662-670
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• 2006

It is well documented that an extract of European mistletoe has a variety of biological effects, such as the stimulation of cytokine production from immune cells, and additional immunoadjuvant activities. While the European mistletoe has been studied intensively, we know less about Korean mistletoe as a therapeutic plant, especially as a possible immunomodulating drug. This study will investigated the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on murine splenocytes to investigate whether VCA acts as an immunomodulator, which could lead to improved immune responses in these cells. The results showed that VCA inhibited cell proliferation at higher concentrations (at 1-8 ng/ml) and enhanced cell proliferation at lower concentrations (at 4-32 pg/ml). Further studies were carried out to determine if the pro-proliferative or anti-proliferative activity exhibited by VCA was correlated with cytokine secretion. Consequently, interferon (IFN)-$\gamma$ secretion was decreased in concanavalin A (ConA)-stimulated murine splenocytes by VCA (4-64 ng/ml), but there was no change in IL-4 levels. This suggests that VCA has the ability to modulate murine splenocyte proliferation and can possibly act on the balance of Th1/Th2 cellular immune responses.

• Molecules and Cells
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• 제22권1호
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• pp.65-69
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• 2006

In murine gastrointestinal myocytes muscarinic stimulation activates nonselective cation channels via a G-protein and $Ca^{2+}$-dependent pathway. We recorded inward cationic currents following application of carbachol ($I_{CCh}$) to murine gastric myocytes held at -60 mV, using the whole-cell patch-clamp method. The properties of the inward cationic currents were similar to those of the nonselective cation channels activated by muscarinic stimulation in other gastrointestinal smooth muscle cells. CCh-induced $I_{CCh}$ and spontaneous decay of $I_{CCh}$ (desensitization of $I_{CCh}$) occurred. Unlike the situation in guinea pig gastric myocytes, desensitization was not affected by varying $[EGTA]_i$. Pretreatment with the PLC inhibitor (U73122) blocked the activation of $I_{CCh}$, and desensitization of $I_{CCh}$ was attenuated in PLC ${\beta}_1$ knock-out mice. These results suggest that the desensitization of $I_{CCh}$ in murine gastric myocytes is not due to a pathway dependent on intracellular $Ca^{2+}$ but to the PLC ${\beta}_1$ pathway.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.55-59
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• 1999

Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccaride (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by $48.7{\pm}4.4%$This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin ($49.51{\pm}2.02%$). at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 $\mu\textrm{g}$/m;; 18hrs) and higenamine (0.001, 0.,01 mM; 18hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.

• 동의생리병리학회지
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• 제21권4호
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• pp.916-920
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• 2007

Flowers of Magnolia denudata has been reported to possess a variety of pharmacological activities. In this study, we investigated the anti-inflammatory effects and mechanism of the water extract of Flowers of Magnolia denudata(MD) in lipopolysacchride (LPS)-mediated inflammatory mediators in murine peritoneal macrophages. MD itself does not have any toxic effects in murine peritoneal macrophages. MD inhibits LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, IL-6 and IL-12 production in murine peritoneal macrophages. Furthermore, we have found that MD inhibited LPS-induced $NF-{\kappa}B$ but not c-Jun N-terminal kinase (JNK), p38 and extracellular signal-ragulated kinase (ERK) activation. These results suggested that MD inhibit LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-12 via suppression of the $NF-{\kappa}B$ activation.

• 동의생리병리학회지
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• 제17권4호
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• pp.991-995
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• 2003

The purpose of this research was to investigate the effects of unripened fruits and ripened fruits of Rubus coreanus Miquel on murine peritoneal macrophages. The 70% ethyl alcohol extracts (20 or 100 mg/kg) of unripened fruits (RCE-I) and of ripened fruits (RCE-II) were administered p.o. once a day for 7 days to mice. RCE-I and RCE-II decreased the phagocytic activity of murine peritoneal macrophages and the production of nitric oxide. Also, RCE-I and RCE-II increased the production of tumor necrosis factor- a from peritoneal macrophages. In general, the immuno-suppressive action of RCE-I on macrophages was more potent than those of RCE-II. These results suggest that the fruits of Rubus coreanus Miquel regulates the non-specific immune response via decrease of phagocytic activity and increase of production of tumor necrosis factor- a from murine peritoneal macrophages.

• 한국수정란이식학회지
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• 제33권4호
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• pp.229-235
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• 2018

Polo-like kinase 1 (Plk1) has been known to be a critical element in cell division including centrosome maturation, cytokinesis and spindle formation in somatic, cancer, and mammalian embryonic cells. In particular, Plk1 is highly expressed in cancer cells. Plk1 inhibitors, such as BI2536, have been widely used to prevent cell division as an anticancer drug. In this study, the fertilized murine oocytes were treated with BI2536 for 30 min after recovery from the oviduct to investigate the effect of down-regulation of Plk1 in the in vivo-fertilized murine embryos. Then, the localization and expression of Plk1 was observed by immunofluorescence staining. The sperm which had entered into the oocyte cytoplasm did not form male pronuclei in BI2536-treated oocytes. The BI2536-treated oocytes showed significantly lower expression of Plk1 than non-treated control group. In addition, alpha-tubulin and Plk1 gathered around sperm head in non-treated oocytes, while BI2536-treated oocytes did not show this phenomenon. The present study demonstrates that the Plk1 inhibitor, BI2536, hinders fertilization by inhibiting the formation of murine male pronucleus.

• IMMUNE NETWORK
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• 제4권3호
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• pp.166-175
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• 2004

Background: Telomerase, a ribonucleoprotein enzyme capable of synthesizing telomeric repeats, attracts attention for its possible role in determining the replicative capacity of normal somatic cells, transformed cells, and cells of the germline lineage. Differently from normal somatic cells with no telomerase activity, normal lymphocytes has been reported to have telomerase activity comparable to that found in transformed cells during development and activation, which substantiate a role in supporting the capacity of lymphocytes for extensive clonal expansion. Methods: Here, in order to define the telomerase regulation in murine T lymphocytes, telomerase activity in cloned murine $CD8^+$ T cells and naive $CD8^+$ T cells isolated from C57BL/6 mice was examined. Next, the regulatory mechanism of telomerase activity at transcriptional and post- translational levels was investigated by determining the expression level of the TERT protein, a key component for telomerase activity. Results: It was demonstrated that telomerase activity was expressed in an inactivated state as well as in an activated state in the murine $CD8^+$ T lymphocytes by using TRAP assay. The increase of telomerase activity was partially dependent on the net increase of TERT expression. Also, telomerase activity was decreased after treatment with protein kinase inhibitors, indicating that telomerase activation was prevented by inhibition of phosphorylation. Conclusion: Therefore, these results suggest that telomerase activity is constitutively expressed in the murine resting T lymphocytes and controlled by both transcriptional regulation and post- ranslational modifications.

• IMMUNE NETWORK
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• 제12권1호
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• pp.27-32
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• 2012

Background: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-${\beta}1$-induced germ line transcript ${\alpha}$ ($GLT{\alpha}$) and IL-4-induced $GLT{\gamma}1$ as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

• ALGAE
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• 제22권4호
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• pp.333-338
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• 2007

A fucoidan, isolated from Korean Undaria pinnatifida spoprophyll (UP-F), was investigated for its immunomodulating activity on murine macrophages and splenocytes, and its activity was compared with that of fucoidan from Fucus vesiculosus (FV-F). Treatment of UP-F resulted in inhibition of the growth of murine macrophage RAW 264.7 cells, but its cytotoxicity was not observed in normal murine splenocytes. FV-F was shown to be highly cytotoxic to both immune cells, and its cytotoxic activity was higher than that of UP-F. Treatment of UP-F induced TNF-α in a dose-dependent manner from two types of macrophages, RAW 264.7 cells and murine peritoneal macrophages. The TNF-α-inducing activity of UP-F was higher than that of FV-F. UP-F also actively induced chemokines (RANTES and MIP-1α) from RAW 264.7 cells. Furthermore, treatment of UP-F gave rise to activation of murine splenocytes to produce cytokine (IL-6) and chemokines (RANTES and MIP-1α), showing significantly higher activity than that of FV-F. These results indicate that UP-F is less cytotoxic to immune cells than FV-F, and possesses immunomodulating activity to produce cytokines and chemokines from macrophages and splenocytes.