• Natural Product Sciences
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• 제3권1호
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• pp.59-70
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• 1997

A rat chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1) has chemotactic and activating properties to neutrophils. Rat kidney epithelioid NRK-52E cells contained 4 ng/ml of ClNC-1 as a basal level and their CINC-1 production was significantly increased by stimulation with lipopolysaccharide (LPS) of E. coli. Maximal induction of ClNC-1 was 58 ng/ml when 3 ${\mu}g/ml$ of LPS was treated to the NRK-52E cells. Inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells by extracts prepared from herbal medicines and wild plants in Korea were analyzed. At the final concentration of 100 ${\mu}g/ml$ , 9 species out of 304 species of herbal extracts exhibited more than 50% of inhibition on the CINC-1 induction. The active extracts prepared from Artemisia argyi, Lythrum salicaria, Machilus thunbergii, Magnolia sieboldii, Nelumbo nucifera, Prunus persica, Rubus coreanus, Sanguisorba officinalis, and Tripterygium regelii have been sequentially fractionated to obtain methylene chloride, ethyl acetate, butanol, and aqueous layers. Among solvent fractions of the active herbal extracts, methylene chloride fractions of Artemisia argyi and Magnolia sieboldii exhibited the highest inhibitory effects on CINC-1 induction in LPS-stimulated NRK-52E cells.

• IMMUNE NETWORK
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• 제21권5호
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• 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.

• IMMUNE NETWORK
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• 제2권1호
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• pp.12-18
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• 2002

Interferon-${\gamma}$ (IFN-${\gamma}$) is well known as a potent inducer in monokine induced by IFN-${\gamma}$ (Mig) mRNA expression. Although lipopolysaccharide (LPS) alone is weakly effective on Mig mRNA expression. the stimulation of LPS and IFN-${\gamma}$ (LPS/IFN-${\gamma}$ simultaneously has been shown to synergize to produce a high level of Mig mRNA in mouse peritoneal macrophages. In this study, interleukin-10 (IL-10) was found to suppress the LPS/IFN-${\gamma}$-induced Mig mRNA expression in cell type- and mouse strain-specific fashion, but IFN-${\gamma}$ alone-induced Mig mRNA was unaffected by IL-10 under identical experimental conditions. The IL-10-mediated suppression of LPS/IFN-${\gamma}$-stimulated Mig mRNA expression was dependent on the concentration of IL-10, and was prevented when the agent was added 2 hours after LPS/IFN-${\gamma}$ treatment. The suppressive action of IL-10 was dependent on a protein synthesis. However, IL-10 did not reduce the stability of LPS/IFN-${\gamma}$-induced Mig mRNA. These data may have important implications for a previously unrecognized role for IL-10 as a regulator of synergistic effect of LPS on the IFN-${\gamma}$-induced expression of the Mig gene in macrophages.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.31-36
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• 1998

Capsular polysaccharides (CPs) from Streeptococcus pneumoniae were examined for the ability to induce secretory responses in a pure population of peritoneal macrophages. The highly purified CPs were able to affect the macrophage, ie, secretion of tumor necrosis factor-alpha (TNF-$\alpha$) and nitrite. As after stimulation with CPs, secretion of TNF-u induced by these CPs reached its maximum within the first few hours of the interaction, while secretion of nitrite was increased with time. In addition, production of TNF-$\alpha$ and nitrite was increased in a dose-dependent manner. In the presence of indomethacin, CP-stimulated TNF-$\alpha$ production was not altered. In contrast, LPS with indomethacin stimulated 24.5% more TNF-$\alpha$ than LPS alone, suggesting that the intracellular signaling processes for TNF production are differentially stimulated by CP and LPS. The results demonstrate that CPs are potent inducer of macrophage secretory activities.

• 한국임상수의학회지
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• 제34권3호
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• pp.172-177
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• 2017

Fucoidan, a cell wall polysaccharide found in the brown seaweed, is reported to have broad-spectrum biological activities. The objectives of this study were to examine the effect of fucoidan on prostaglandin $E_2$ ($PGE_2$) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated porcine peripheral blood mononuclear cells (PBMCs) and to determine whether these effects are involved in Akt activation. The levels of $PGE_2$ production in the culture supernatants from PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) kit and the levels of COX-2 mRNA were measured by real time polymerase chain reaction (RT-PCR). Akt activity was determined by Western blot analysis. Fucoidan in LPS-$na{\ddot{i}ve}$ PBMCs has no effect on $PGE_2$ production and COX-2 mRNA expression. Furthermore, fucoidan does not affect Akt activation in LPS- $na{\ddot{i}ve}$ PBMCs. However, $PGE_2$ production and COX-2 mRNA expression on PBMCs were remarkably enhanced by LPS stimulation. Akt activity was also increased by LPS. Increasing effects of $PGE_2$ production and COX-2 mRNA expression in PBMCs induced by LPS were suppressed by addition of fucoidan. In addition, fucoidan reduced an increase in Akt activity in LPS-stimulated PBMCs. These results suggested that fucoidan exerts potent anti-inflammatory properties by suppression of $PGE_2$ production, COX-2 mRNA expression and Akt activation in LPS-stimulated PBMCs.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.99-99
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• 2002

In the present study, the potent lipopolysaccharide (LPS)-mimetic stimulation of B cells and macrophages by hot water extract from Salicornia herbacea (S. europeae L.) is described. The extract activated spleen cells to proliferate in a dose-related manner as measured by [$^3$ H)-thymidine incorporation response.(omitted)

• 한국식품영양학회지
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• 제20권3호
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• pp.259-264
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• 2007

Ginger(Zingiber officinale Roscoe) has been used as a raw material in many various traditional preparations since the ancient times. As a component of traditional health products, ginger is known to be effective as an appetite enhancer, and has anti-cold and anti-inflammatory activities. This study was performed to investigate the immunomodulative effects of Zingiber officinale Roscoe in mice, using ex vivo experiments. In order to elucidate ginger's immunomodulative effects of Ginger, water extracts were orally administered to mice, and isolated macrophages were used as the experimental model. To identify the ex vivo effects, six to seven week old Balb/c mice were fed a chow diet ad libitum and the ginger water extracts were administered orally every other day for two or four weeks at two different concentrations(50 and 500 mg/kg b.w.). The results show that IL-IO and $IFN-{\gamma}$ were detected in the 500 mg/kg b.w. supplemented group with LPS stimulation in all cases. Also, the $IFN-{\gamma}$ /IL-10 ratio ranged from 3~5 with mitogen stimulation such as Con A and LPS. In conclusion, this study suggests that ginger extracts may enhance the immune function by regulating the cytokine(IL-10 and $IFN-{\gamma}$) production capacity of activated macrophages in mice.

• Animal cells and systems
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• 제7권1호
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• pp.57-62
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• 2003

Flounder B lymphocytes isolated from different tissues were studied in terms of cell proliferation, apoptosis and the effects of cortisol on these processes. B lymphocytes, isolated from the flounder head kidney and spleen, were characterized by higher proliferation and lower intracellular calcium ($Ca^2$) response to lgcrosslinking compared with peripheral blood B lymphocytes. Cortisol induced high levels of apoptosis (150% of control levels) in peripheral blood B lymphocytes, in combination with a stimulatory LPS signal. Head kidney and to a lesser extent spleen B lymphocytes, although less sensitive than their equivalent in peripheral blood, underwent cortisol-induced apoptosis irrespective of extra stimulation up to 142% of control levels. Also proliferation with and without LPS stimulation was suppressed by cortisol (compared to plasma values measured during stress conditions) that is effective in inducing a significant increase in apoptosis in all three populations of B-cells, suggesting that cortisol may be important for immunoregulation in both stressed and non-stressed conditions. This implies possible severe impact of stress on lymphocyte development and activity, Different sensitivity of B-cells to the corticosteroid, with respect to developmental stage and activity, may prevent excessive and long lasting depletion of B-lymphocytes.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.36-44
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• 2006

진통과 해열작용을 가진 NSAIDs는 소화기계에 대한 부작용 때문에 COX-2 선택성 억제제로 대체되고 있다. 그러나 COX-2 선택적 억제제는 심혈관계에 대한 부작용이 보고되고 있어 혈관 평활근에 대한 직접적인 연구가 필요하다. 이에 본 연구에서는 혈관 반응성에 미치는 celecoxib와 aspirin, indomethacin의 영향을 비교 분석하였다. 또한 COX-1, COX-2 단백질 발현에 대한 indomethacin과 NO 공여제의 영향을 조사하였다. Phenylephrine 유발 수축반응에서 전처치 된celecoxib, indometacin, aspirin 순서로 혈관 반응성을 증가시켜, cyclooxygenase를 억제하면 혈관 수축성물질에 대한 반응성이 커질 수 있음을 나타낸다. 이중 cyclooxygenase에 대해 비가역적으로 강한 억제를 나타내는 aspirin이 제일 강한 효과를 나타내어 여기에 대한 연구는 더 필요할 것으로 생각된다. 혈관평활근 세포의 COX-2 단백질 발현은 indomethacin과 SNP, NOR-3 처치에 의해 증가되었으며, LPS를 이용하여 혈관염증을 유발 시키는 경우 혈관평활근 세포의 COX-2 단백질 발현이 증가되었고, 이 상태에서 SNP $100{\mu}M$ 전처치로 COX-2 단백질 발현을 감소되었으며, NOR-3 $100{\mu}M$은 COX-2 단백질 발현을 증가시켰다. LPS 유도 nitrite 생성에서 NOR-3는 SNP 보다 더 많은 nitrite를 생성시켰다. 이는 혈관의 수축반응에서 aspirin은 강한 상승작용을 유발하고, 혈관평활근 세포의 COX-2 발현은 NO 공여제, 혈관염증 유무에 따라 차이가 있는 것을 나타낸다.