• Archives of Pharmacal Research
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• v.22 no.3
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• pp.267-273
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• 1999

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-\gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-\gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$\alpha$ or the inhibition of NO Production, TNF-$\alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-\gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-\gamma$ contained both TNF-$\alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$\alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-\gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.

• YAKHAK HOEJI
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• v.60 no.1
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• pp.21-28
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• 2016

Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.

• The Korean Journal of Food And Nutrition
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• v.27 no.4
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• pp.603-608
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• 2014

Pleurotus ostreatus have been used as a traditional remedy and food source. Its anti-inflammatory, anti-oxidation effects have been previously reported. The production of cytokines (IL-$2{\beta}$, IFN-${\gamma}$, and TNF-${\alpha}$) secreted by LPS- and non LPS-stimulated macrophages, were detected by ELISA assay using a cytokine kit. Mouse splenocytes proliferation increased with Pleurotus ostreatus water extracts supplement at 5, 10, 50, 100, 250, 500, $1,000{\mu}g/mL$ after a 48hr pre-treatment with the mitogen (ConA or LPS). The cytokine production (IL-$2{\beta}$, IFN-${\gamma}$, and TNF-${\alpha}$), measured by a cytokine ELISA kit, increased on water extracts supplementation. This in vitro study suggested that supplementation with Pleurotus ostreatus water extracts may enhance the immune function by regulating the splenocyte proliferation and enhancing cytokine production.

• The Korean Journal of Food And Nutrition
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• v.30 no.3
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• pp.510-514
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• 2017

Plantago asiatica L., observed frequently in East Asia, is a known herb used in traditional medical remedies several studies report that P. asiatica L has anti-inflammatory and antioxidant effects. To determine the production of cytokines (IL-2, $IFN-{\gamma}$, and $TNF-{\alpha}$) induced by lipopolysaccharide (LPS) and non-LPS-stimulated macrophages, an ELISA assay was conducted using cytokine kits. Mice splenocytes were cultured for 48 h with various concentrations of P. asiatica L. (5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$) or with mitogens (ConA or LPS). P. asiatica L. increased the proliferation of mice splenocytes, especially under the condition of its concentration ranging from 250 to $1,000{\mu}g/mL$. In addition, Plantago asiatica L. notably induced cytokine production of (IL-2, $IFN-{\gamma}$, and $TNF-{\alpha}$) at its concentration of $250{\sim}500{\mu}g/mL$. These results suggest that supplementation with P. asiatica L. water extracts may play a potential role in enhancing immune function by mediating splenocyte proliferation and cytokine production through its anti-inflammatory activit.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.184-190
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• 2006

We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) on the in vitro production of cytokines by splenocytes and peritoneal macrophages isolated from C57BL/6 mice. Peritoneal macrophages and splenocytes were incubated with various concentrations of RGMeOH in the presence of $10\;{\mu}g/ml$ of lipopolysaccharide (LPS) $1\;{\mu}g/ml$ of concanavalin A (Con A) for cytokine assay, These results showed that RGMeOH remarkably attenuated LPS-increased production of $TNF-{\alpha}$ but not IL-6 by peritoneal macrophages and enhanced LPS-stimulated production of IL-10 in a dose-dependent manner RGMeOH significantly augmented the LPS- or Con A-stimulated production of IL-2 and $IFN-{\gamma}$ by splenocytes. These findings suggest that RGMeOH may attenuate inflammatory responses through down-regulation of $TNF-{\alpha}$ and up-regulation of IL-10, and that RGMeOH may up-regulate cell-mediated immune responses through increase in IL-2 and $IFN-{\gamma}$ production.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.209-214
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• 2004

Lead has long been considered as a toxic environmental pollutant that severely damages the central nervous system. In various neurogenerative diseases, actrocytes become activated by proinflammatory cytokines. In the present study, we investigated whether lead (Pb$^{2+}$) affects inducible nitric oxide synthase (iNOS) expression in activated glial cells. Rat primary glial cells were stimulated with lipopolysaccharide (LPS, 1 ${\mu}$g/ml) plus IFN$_{\gamma}$(100 U/ml). Pre-treatment of Pb$^{2+}$ increased nitric oxide (NO) production in LPS/IFN$_{\gamma}$-stimulated glial cells. Lead itself, however, suppressed the basal production of NO in control glial cells. Addition of the iNOS inhibitors L-NAME (1 mM) and L-NNA (800 ${\mu}$M) prevented the Pb$^{2+}$-induced increase in NO production. Western blot analysis showed that pre-treatment of Pb$^{2+}$ augmented LPS/IFN$_{\gamma}$-induced increase in iNOS immunoreactivity, which was well correlated with the increased NO production. In addition, pre-treatment of Pb$^{2+}$ synergistically increased the iNOS mRNA expression induced by LPS and IFN${\gamma}$. The present results indicate that lead intoxication adversely affect brain function by potentiating iNOS expression and NO production in activated glial cells observed in various neurodegenerative diseases.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.19-27
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• 2002

Objective : This study was designed to investigate the effect of Hyeolbuchukeo-tang (HCT) on NO production and the molecular mechanism of NO production modulated by HCT in the primary VSMC (vascular smooth muscle cells). Method : Primary VSMC was established from aorta and cultured VSMC used in this study. NO production of VSMC was assayed by Griess reagent and the expression of iNOS gene was assayed by Western, RT-PCR. Result : $TNF-{\gamma}$ induced NO production, but $IFN-{\gamma}$ or HCT alone did not induce NO production in cultured VSMC. However, $IFN-{\gamma}$ or HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC in a time- and dose-dependent manner. $TNF-{\gamma}$ induced the iNOS gene expression corresponding to NO production in $TNF-{\gamma}-treated$ VSMC. HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC by about 20%, but HCT did not increase the level of iNOS mRNA in $TNF-{\gamma}-treated$ VSMC. HCT slightly increased the level of iNOS protein in $TNF-{\gamma}-treated$ VSMC. Calcium ionophore A23187 decreased NO production in $TNF-{\gamma}-treated$ VSMC, but HCT attenuated the effect of A23187. Conclusion : As NO is deeply involved in the development of arteriosclerosis and dilation of blood vessels, drugs or chemicals modulating NO production in VSMC could be used for preventing and treating arteriosclerosis. Considering the effect of HCT on the modulation of NO production in VSMC, MCT has a potential capacity for preventing and treating diseases of the circulation system including arteriosclerosis.

• The Journal of Korean Medicine
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• v.24 no.1
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• pp.54-64
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• 2003

Objective : To investigate immune enhancing effects of Boummyunyuck-dan (BMD) Methods : In this study I investigated the effect of BMD on cell proliferation and viability. In addition, I investigated production of cytokines (IL-2, IL-4 and $IFN-{\gamma}$), NO, and $TNF-{\alpha}$ in human T-cell leukemia, MOLT-4 cells. The cells were cultured for 24h in the presence or absence of BMD. Result : BMD increased the cell viability by 15% (P<0.05) and enhanced IL-2, IL-4 and $IFN-{\gamma}$ production compared with media control in a dose-dependent manner (P<0.01) at 24h. BMD also increased mRNA and protein expression levels of $IFN-{\gamma}$ in MOLT-4 cells. In addition, I also assessed the effects of BMD on production of NO and $TNF-{\alpha}$ from the peritoneal macrophages because NO and $TNF-{\alpha}$ as a potent macrophage-derived immune reaction regulatory molecule has received increasing attention. However, BMD had no effect on NO and $TNF-{\alpha}$ production in the cells. Conclusion : These data indicate that BMD has some immune-enhancing effect, and that its action may be due to the proliferation and cytokine production of T cells.

• Journal of Nutrition and Health
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• v.24 no.2
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• pp.97-103
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• 1991

The increase in alcohol consumption level has been noticed in Korea recently. Alcohol appreciably inhibits cell mediated immunity and this may contribute to the high prevalence of serious infection such as pulmonary tuberculosis among alcoholic subjects. The present study was undertaken to examine the effect of ethanol on the cyclooxygenase metabolites of human monocyte in vitro. Monocytes were activated with 800 units of gamma interferon(IFN-${\gamma}$) for 3 days following apply of Ficool-hypaque density gradient and gelatin coated flasks for separation of monocytes. Ethanol with addition of 100mM, 300mM and 600 mM for 30 minutes to 106 monocytes with/without previous IFN-${\gamma}$ treatment caused a dose dependent decrease in the production of thromboxane B2, 6-keto-PGE1$\alpha$ and PGE2 by radioimmunoassay at 6 hours after ethanol treatment. Quite different from the findings after 6 hours there was dose dependent increase in three prostaglandins without IFN-${\gamma}$ treatment after 24 hours of incubation. With previous treatment of IFN-${\gamma}$ reduced productions of three prostaglandins at 24 hours than control is spite of ethanol stimjulation. These findings show that IFN-${\gamma}$ can inhibit alcohol induced derangement of arachidonic acid metabolism of monocytes.