• The Korea Journal of Herbology
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• v.22 no.4
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• pp.233-238
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• 2007

Objectives : Scutellariae Radix (Hwanggeum in Korean) is the root of Scutellaria baicalensis Georgi. Scutellariae Radix is well known to be used as a medicine for common cold, upper respiratory infections, and to strengthen and regulate the immune system and anemia etc. Little is understood about the roles of Scutellariae Radix in the cytokine and chemokine secretion by immune cells. This study was designed to find out the effects of Scutellariae Radix on the cytokine and chemokine secretion in human mast cells (HMC-1). Methods : We treated hwanggeum according to consistency on HMC-1 and measured cytokines and chemokines levels using flow cytometry CBA system. Results : In hwanggeum treated group, the expression of interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), chemokine (C-X-C motif) ligand 9 (CXCL9, MIG), interleukin 8 (IL-8), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 10 (IL-10), and interferon ${\gamma}$ (IFN-${\gamma}$) were decreased significantly. Conclusion : These results suggest that hwanggeum may support some of immune diseases by means of amiliorating some chemokines or cytokines such as IP-10, MCP-1, MIG, IL-8, IL-2, IL-4, IL-5, IL-10, and IFN-${\gamma}$.

• IMMUNE NETWORK
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• v.9 no.5
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• pp.192-202
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• 2009

Background: Little information is available the role of Nitric Oxide (NO) in host defenses during human tuberculosis (TB) infection. We investigated the modulating factor(s) affecting NO synthase (iNOS) induction in human macrophages. Methods: Both iNOS mRNA and protein that regulate the growth of mycobacteria were determined using reverase transcriptase-polymerase chain reaction and western blot analysis. The upstream signaling pathways were further investigated using iNOS specific inhibitors. Results: Here we show that combined treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) and Interferon (IFN)-${\gamma}$ synergistically enhanced NO synthesis and iNOS expression induced by Mycobacterium tuberculosis (MTB) or by its purified protein derivatives in human monocyte-derived macrophages. Both the nuclear factor-${\kappa}B$ and MEK1-ERK1/2 pathways were indispensable in the induction of iNOS expression, as shown in toll like receptor 2 stimulation. Further, the combined treatment with 1,25-D3 and IFN-${\gamma}$ was more potent than either agent alone in the inhibition of intracellular MTB growth. Notably, this enhanced effect was not explained by increased expression of cathelicidin, a known antimycobacterial effector of 1,25-D3. Conclusion: These data support a key role of NO in host defenses against TB and identify novel modulating factors for iNOS induction in human macrophages.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.568-575
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• 2000

Background : Cytokines are chemical mediators that control and modulate many inflammatory processes. They work in different fashions in a variety of diseases. Discriminating between malignant effusion, tuberculous effusion, and parapneumonic effusion are crucial from the clinical view-point in Korea. In the current study, interferon-gamma (IFN-${\gamma}$), soluble interleukin-2 receptor (IL-2R), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured for this purpose. Methods : Pleural fluids from patients with malignant disease, tuberculosis, parapneumonic effusion and lung empysema were collected and gauged using commercial ELISA kits. Results : 34 patients were enrolled in this study. Among these 15 cases were malignant effusions, 12 were tuberculosis pleurisy and 7 were parapneumonic effusion and lung empyema. The levels of cytokines measured in this study were as follows, in order of frequency, malignant effusion, tuberculous effusion, parapneumonic effusion and lung empyema. The levels of INF-${\gamma}$ were higher in tuberculous effusion than in malignant or parapneumonic effusion ($295.5{\pm}585.5$ vs. $16.7{\pm}50$ vs. $10.0{\pm}0$ pg/ml, p>0.05). The levels of IL-2R were higher in tuberculous effusion than in malignant or parapneumoruc effusion ($7423.5{\pm}3752.8$ vs. $3247.4{\pm}1713.3$ vs. $3790.2{\pm}3201.1$ pg/ml, p<0.05). No significant differences were found in the levels of IL-6 between the groups ($600{\pm}12.8$ pg/ml in malignant effusion, $556.4{\pm}161.7$ pg/ml in tuberculous effusion, $514.4{\pm}224.8$ pg/ml in parapneumoruc effusion). IL-10 levels were higher in parapneumoruc effusion than in malignant or tuberculous effusions ($98.4{\pm}141.7$ vs. $28.2{\pm}55.5$ vs. $11.3{\pm}11.7$ pg/ml, p<0.05). Conclusion : These results suggest that the measurement of IL-2R levels in pleural fluids may be a useful means of differentiating between tuberculous effusion and pleural effusions of other origins, and that the measurement of IL-10 levels in pleural fluids may be useful to differentiate between parapneumonic effusion and pleural effusions of other origins.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.971-976
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• 2008

Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-$Gu{\acute{e}}rin$ (BCG)-vaccinated population. The object was to perform a blood test $QuantiFERON^{(R)}$-TB Gold In Tube (QFT-G IT) based on the detection of interferon-$\gamma$ ($IFN-{\gamma}$) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (${\kappa}=0.39$). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood $IFN-{\gamma}$ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1279-1284
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• 2008

When cheonggukjgang was manufactured using a Bacillus subtilis CH10-1 starter culture, a short-term fermentation for 14-18 hr appeared to be the optimal for the raw cheonggukjang to avoid the formation of a bitter taste and to contain a high concentration of free sugars, whereas a long-term fermentation for more than 4 days was the optimal for the cheonggukjang for stew in order to contain a high concentration of free amino and organic acids, which are responsible for sweet, savory, and bitter tastes present in stewed cheonggukjang, During activation of murine splenic T cells with phytohemagglutinin (PHA), the presence of either poly-$\gamma$-glutamic acid ($\gamma$-PGA) or partially hydrolyzed $\gamma$-PGA resulted in reduction in the level of interferon-$\gamma$ production and enhancement in the level of interleukin-5 production, possibly due to suppression of Th1 activity and augmentation of Th2 activity. Taken together these results indicate that the raw cheonggukjang and the cheonggukjang for stew are different in their quality and taste as well as immunomodulating activity.

• 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.44 no.5
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• pp.448-454
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• 2000

Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.280-289
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• 1998

Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-$\gamma$, TNF-$\alpha$ are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-$\gamma$, and there are two studies in Korea. But the diagnostic values of IFN-$\gamma$ in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN-$\gamma$ with those of CEA and ADA, and to determine the sensitivity and specificity of IFN-$\gamma$ in Korean, we mesured IFN-$\gamma$, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN-$\gamma$ level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN-$\gamma$ and ADA ($832.6{\pm}357.2$ pg/ml and $82.5{\pm}25.9$ U/L, respectively) than those of malignant pleural effusion ($2.6{\pm}8.0$ pg/ml and $19.2{\pm}10.9$ U/L, respectively) (p<0.01). Malignant pleural effusions showed higher median value (102.2 ng/ml) than tubercalous pleural effusions (1.8 ng/ml) (p<0.01). The sensitivities of IFN-$\gamma$, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-$\gamma$, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN-$\gamma$ level. Conclusion: This study showed that IFN-$\gamma$ test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

• Molecules and Cells
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• v.39 no.5
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• pp.410-417
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• 2016

During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma ($IFN-{\gamma}$) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether $IFN-{\gamma}$ can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether $IFN-{\gamma}$ affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of $IFN-{\gamma}$ on milk synthesis in primary BMECs in vitro. The results showed that $IFN-{\gamma}$ significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following $IFN-{\gamma}$ treatment, and the inhibition of autophagy can improve milk protein and milk fat synthesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis confirmed that $IFN-{\gamma}$ mediated autophagy by depleting arginine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor $2{\alpha}$ ($eIF2{\alpha}$) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate $IFN-{\gamma}$-induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the $IFN-{\gamma}$-induced decrease in milk quality but also a useful therapeutic approach for $IFN-{\gamma}$-associated breast diseases in other animals and humans.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.127-133
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• 2017

Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.