• Advances in Traditional Medicine
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• v.3 no.1
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• pp.34-39
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• 2003

We investigated the immune enhancement effects of JaSaengHwan (JSH). The forced swimming test (FST) has been used as a screening model for new immune enhancement agents. We found that JSH (0.1 mg/ml) significantly reduced the immobility time in the FST compared to the control. Also, we investigated the effect of JSH on the proliferation of T cell and production of cytokines in human T-cell line, MOLT-4 cells and mouse peritoneal macrophages. JSH (1 mg/ml) significantly increased the cell proliferation by $46.78{\pm}6.41%$ (p<0.05) and also significantly increased the interleukin (IL)-2, IL-4 and interferon $(IFN)-{\gamma}$ production compared with media control (about 2-fold for IL-2, 3-fold for IL-4 and 1.5-fold for $IFN-{\gamma}$, p<0.05) at 24 h. In addition, JSH increased the production of IL-12 on the mouse peritoneal macrophages (by 3.6-fold for IL-12, p<0.05). In conclusion, these data indicate that JSH may have an immune-enhancement effect.

• CELLMED
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• v.2 no.3
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• pp.27.1-27.6
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• 2012

Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and $I{\kappa}B$ kinase-beta (IKK-${\beta}$) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-${\beta}$ for the first time. When HRG was used in combination with recombinant interferon-${\gamma}$ (rIFN-${\gamma}$), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-${\gamma}$ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). In addition, the treatment of peritoneal macrophages with rIFN-${\gamma}$ plus HRG caused significant increases in tumor necrosis factor (TNF)-${\alpha}$ mRNA expression and production. Because NO and TNF-${\alpha}$ play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-${\kappa}B$. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-${\alpha}$ from rIFN-${\gamma}$-primed macrophages and suggest that Rip2/IKK-${\beta}$ plays a critical role in mediating these immune regulatory effects of HRG.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.117-124
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• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• International Journal of Oral Biology
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• v.31 no.2
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• pp.67-72
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• 2006

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of $30{\mu}M$ SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration($3{\mu}M$) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS 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 LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.7-12
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• 2005

GyeongshinhaeGihwan T1 (GGT1) is a newly developed oriental medicine to help weight control. We investigated nitric oxide production and cytokine secretion in mouse peritoneal macrophages. According to recent reports, macrophages are participated in fat accumulation and closely related with obesity. In this study, using mouse peritoneal macrophages, we have examined whether GGT1 affects the production of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interleukin (IL)-12 by the stimulation of interferon-${\gamma}$ and lipopolysaccharide (LPS). GGT1 inhibits LPS-induced NO production in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthese protein. We also found that GGT1 inhibits pro-inflammatory cytokines, TNF-${\alpha}$ and IL-12 production. In mouse embryo preadipocyte 3T3-L1, GGT1 reduced the viability in a dose-dependent manner. These findings suggest that GGT1 may have potential effects in preventing and controlling adipogenesis and obesity.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.369-373
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• 2006

Water extracts obtained from cultured mountain ginseng (CMG) were evaluated for their ability to stimulate immune cells and inhibit cancer cell proliferation. The lymphocyte subpopulation in mouse splenocytes in vivo was significantly increased by the administration of the CMG extract (27.4 mg/mouse). Interleukin-2 and ${\gamma}$-interferon in the mice serum increased up to 30% in CMG extract-treated mice. At a concentration of 1.37 mg/mL, nitric oxide increased up to 400% in the macrophage cell line treated with CMG extract. The CMG extract significantly retarded the proliferation of human acute promyelocytic (HL60), human histiocytic (U937), and mouse lymphocytic (L1210) leukemia cell lines in vitro at concentrations over 2.74-13.7 mg/mL. In addition, CMG extract treatments (1.37 mg/mL and 2.74 mg/mL) lead to the increased expression of the p53 gene and protein in cultured U937 leukemia cell lines. These results indicate that water extracts of CMG are capable of both immune cell stimulation and cancer cell growth inhibition.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.306-313
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• 2017

Purple bamboo salt (PuBS) is commonly used as a medicinal food in Korea and has beneficial potentials such as antioxidant and anti-inflammatory effects. Rubus coreanus is called Bokbunja, which is used as a traditional medicine for treating asthma, impotence, and allergic diseases in Korea. The aim of present study was to investigate the immunostimulatory effect of PuBS composed with Rubus coreanus (PuBS-R). We performed comparative analysis between PuBS and PuBS-R in Raw264.7 cells, which is a mouse macrophage cell line, and peritoneal macrophages isolated primarily from the mouse peritoneal cavity. We evaluated cytotoxicity and the immune cytokine response in PuBS- and PuBS-R-treated cells. Both PuBS and PuBS-R did not have any cytotoxicity in Raw264.7 cells up to $500{\mu}g/mL$. Gene and protein levels of immune cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interferon-{\gamma}$ ($IFN-{\gamma}$), interleukin (IL)-10, and IL-12 were significantly elevated by PuBS-R more than PuBS in Raw264.7 cells. Moreover, we evaluated the immunostimulatory effects of PuBS-R on mouse primary peritoneal macrophages. Protein levels of inducible nitric oxide synthase, $TNF-{\alpha}$, $IFN-{\gamma}$, IL-10, and IL-12 were significantly higher in PuBS-R-treated peritoneal macrophages than PuBS-treated peritoneal macrophages. These results suggest the potential immunostimulatory effect of PuBS-R for immunity against harmful infection.

• BMB Reports
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• v.52 no.4
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• pp.289-294
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• 2019

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

• The Korean Journal of Food And Nutrition
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• v.24 no.1
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• pp.65-70
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• 2011

This study was performed to investigate the in vitro effect of a corn water extract on immune function. Splenocyte proliferation was determined by the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl terazolium bromide) assay after preparing asingle cell suspension. Production of macrophage-secreted interleukin(IL)-$1{\beta}$, IL-6, and interferon(IFN)-${\gamma}$, was detected by ELISA using a cytokine assay kit. After a 48-hr incubation with mitogens(ConA or lipopolysaccharide), mice splenocyte proliferation increased with the addition of a corn water extract supplement at 10, 50, 100, 250, 500, or $1,000\;{\mu}g/m\ell$. Production of IL-$1{\beta}$, IL-6, and IFN-${\gamma}$ increased in treatments supplemented with the corn water extract. In an in vitro study, splenocyte proliferation increased when $50\sim1,000\;{\mu}\ell/m\ell$ corn water extract was added. In an ex vivo experiment, the highest production of cytokines by activated peritoneal macrophages was observed in mice orally administered 500 mg/kg body weight/day.