• The Korean Journal of Food And Nutrition
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• v.22 no.1
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• pp.69-74
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• 2009

Codonopsis lanceolatae have been used as one of the traditional remedies as well as food source. We previously reported that in vitro supplementation of Codonopsis lanceolatae water extracts enhanced the splenocytes proliferation compared to the control group. This study, the combined immunomodulative effect of water extract Codonopsis lanceolatae was Seven to eight weeks old mice(balb/c) was fed ad libitum on chow diet and water extract of Codonopsis lanceolatae was orally administrated every other day for four weeks at two different concentrations(50 and 500 mg/kg B.W.). The production of cytokine(IL-2, IL-10 and IFN-${\gamma}$), secreted by macrophages stimulated with LPS or not, were detected by ELISA assay using the cytokine kit. The result of ex vivo study showed that the IL-2, IL-10 and IFN-${\gamma}$ was detected at 500 mg/kg B.W. supplementation group with LPS stimulation in all cases. Also, ratio of IFN-${\gamma}$, IL-10 was the range of 3${\sim}$7 with mitogen stimulation such as Con A and LPS. In conclusion, this study suggests that Codonopsis lanceolatae extracts may enhance the immune function by regulating the cytokine(IL-2, IL-10 and IFN-${\gamma}$) prodution capacity by activated macrophages in mice.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.702-709
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• 2003

Purpose : $IFN{\gamma}$ sentitizes many tumor cells to $TNF{\alpha}$ and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that $IFN{\gamma}$ and $TNF{\alpha}$ synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of $IFN{\gamma}$ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/CD95L autocrine circuit. In this study, we examined whether $IFN{\gamma}$ could affect $TNF{\alpha}$ and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. Methods : CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant $IFN{\gamma}$, $TNF{\alpha}$ and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V-PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. Results : $IFN{\gamma}$ or $TNF{\alpha}$ alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of $IFN{\gamma}$ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were non-specifically enhanced after treatment of $IFN{\gamma}$ without relation to sensitivity to $TNF{\alpha}$ and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of $TNF{\alpha}$ and CH-11-mediated apoptosis by $IFN{\gamma}$ in only sensitive cell lines. Conclusion : $IFN{\gamma}$ induced sensitization of $TNF{\alpha}$ and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.336-344
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• 2006

Objects : This study has been carried out to assess the effects of the variable herbs on $IFN-{\gamma}$ secretion in the mouse spleen cell. Methods : 202 kinds of herb extracts were used to evaluate the $IFN-{\gamma}$ secretory distinction by each $1{\mu}g/ml$ and $10{\mu}g/ml$ density of water. All experimental herbs were grouped by oriental herbalogical method. But each herb had its independent variables. Results : The secretions increased in 20% of all herbal water. The density differences also make different effects on the secretion of $IFN-{\gamma}$. The secretion of IFN-${\gamma}$ inclosed in some kinds of herbs of IFN-${\gamma}$. It has representatively increased in Imperaetae Rhizoma(白茅根) of $1{\mu}g/ml$ and Notopterygii Rhizoma(羌活)of $10{\mu}g/ml$. $IFN-{\gamma}$ incresed in 12 kinds of heybs of both densities. The secretion of $IFN-{\gamma}$ decreased in some kinds of herbs of $IFN-{\gamma}$. It has representatively decreased in Moutan Radicis Cortex(蘇丹皮) of $1{\mu}g/ml$ and Angelicae Radix(富歸尾) of $10{\mu}g/ml$. $IFN-{\gamma}$ decreased in 18 kinds of herbs of both densities. In t oriental herb group, The secretion of $IFN-{\gamma}$ increased in Bang-Hyang-Hwa-Sup group(芳香化濕藥), He-Pyo group(解表藥), I-Su-Sam-SuP group(利水渗) The secretion of $IFN-{\gamma}$ decreased in Gu-Chung group(驅蟲藥), An-Sin group(安神藥). Su-Sap group(收澁) On-Li group(溫裏藥), I-Gi group(利氣藥). Conclusions : The result of this study will not only broaden applications of oriental medicine to biological therapy, but also form the basis of oriental medical therapy to find out the meaning of oriental classification.

• The korean journal of orthodontics
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• v.23 no.2 s.41
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• pp.229-248
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• 1993

[ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.

• Journal of Microbiology and Biotechnology
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• v.10 no.5
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• pp.599-605
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• 2000

Lipopolysaccharide (LPS) is responsible for the tissue injury that occurs following the invasion of multicelluar organisms by Gram-negative microbes. The effect of LPS on IFN-$\gamma$-induced chemokine Mig gene expression in mouse peritoneal macrophages was investigated. Very little Mig mRNA was detectable upon exposure to LPS without IFN-$\gamma$. Although LPS alone is only minimally effective, LPS plus IFN-$\gamma$ synergized to produce a high level of Mig mRNA in the peritoneal macrophages. This synergy was not dependent on a new protein synthesis, and was not controlled at the level of the gene transcription. Futhermore, LPS did not increase IFN-$\gamma$-induced Mig mRNA stability. Accordingly, it is suggested the LPS may synergize the expression of IFN-$\gamma$-induced Mig mRNA through a process that depends on a pretranscriptional level or concurrent Mig mRNA translation.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.186-192
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• 2005

Background : Diagnosis of tuberculous pleurisy is sometimes difficult using conventional diagnostic methods. We have investigated the utility of pleural fluid cell $IFN-{\gamma}$ production assay in the diagnosis of tuberculous pleurisy. Methods : We prospectively performed pleural fluid cell $IFN-{\gamma}$ production assay in 39 patients with tuberculous pleural effusions (TPE) and in 26 patients with nontuberculous pleural effusions (NTPE) (13 malignant pleural effusions and 13 parapneumonic effusions). Pleural fluid cells were cultured in DMEM media and stimulated with purified protein derivatives (PPD), and phytohemagglutinin (PHA) for 24 hr. The amount of $IFN-{\gamma}$ released in the culture supernatant was quantitated by $IFN-{\gamma}$ ELISA assay. We have also measured adenosine deaminase (ADA) activities and $IFN-{\gamma}$ concentrations in the pleural fluid. Results : 1) The pleural fluid levels of ADA activity and $IFN-{\gamma}$ concentrations were significantly higher in TPE than NTPE (p<0.01). 2) $IFN-{\gamma}$ production in TPE cells stimulated by PPD ($755,266{\pm}886,636pg/ml$) was significantly higher than NTPE cells ($3,509{\pm}6,980pg/ml$) (p<0.01). By considering the fact that $IFN-{\gamma}$ concentrations over 10,000 pg/ml is a criteria for the diagnosis of TBE, sensitivity and specificity of the test were 97.4 and 92.3%, respectively. 3) The ratios of $IFN-{\gamma}$ production by the stimulation with PPD and PHA (PPD/PHA) were significantly higher in TPE cells ($59{\pm}85$) than NTPE cells ($5{\pm}18$)(p<0.01). Considering the criteria for the diagnosis of TBE as PPD/PHA ratio over 5, sensitivity and specificity of the test were 76.9 and 92.3%, respectively. Conclusion : Pleural fluid cell $IFN-{\gamma}$ production assay may be useful for the diagnosis of tuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.301-310
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• 1998

Background: Cell mediated immune response mediated by interaction between CD4+ T lymphocytes and macrophagies is thought to play an important role in tuberculous pleurisy. This interaction is dependent on the interplay of various cytokines. The immunologic response of tuberculous pleurisy is thought to depend on the balance between helper T cell(Th1) cytokine Interleukin-12, Interferon gamma and Th2 cytokine IL-4, IL-10. To understand immunologic mechanism in tuberculous pleurisy and evaluate diagnostic value of these cytokines, the concentrations of Th1 cytokine IL-12, IFN -$\gamma$ and Th2 cytokine IL-10 were measured in tuberculous pleurisy and malignant pleural effusion group. Material and Methods: The concentrations of IL-10, IL-12 and IFN-$\gamma$ were measured by ELISA method in pleural fluids and serums of 20 patients with tuberculous pleurisy and 20 patients with malignant pleural effusion ADA activities were measured by spetrophotomery in pleural fluids of both groups. Results: In tuberculous pleurisy, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL and $420.4{\pm}285.9$ pg/mL. These were significantly higher than that of serum, $21.2{\pm}60.9$ pg/mL, 194.5 pg/mL, $30.1{\pm}18.3$ pg/mL respectively(p< 0.01). In malignant pleural effusion, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL and $30.5{\pm}54.8$ pg/mL respectively. Compared with that of serum ($43.4{\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL), only IL-10 was significantly higher (p<0.001), but IL-12, IFN-$\gamma$ were not significant. In tuberculous pleural effusion compared with malignant pleural effusion, the concentration of IL-12, IFN-$\gamma$, ADA were significantly higher (p=value 0.046, <0.001, <0.001), but IL-10 was not significant. For differential diagnosis of tuberculous pleurisy from malignant pleural effusion, using cut-off value of IL-12, IFN-$\gamma$, ADA as 300 pg/mL. 100 pg/mL, 45 U/L, the sensitivity/specificity were 60%/70%, 90%/87.5%, 85%/90% respectively. Conclusion: In tuberculous pleurisy, IL-10, IL-12 and IFN-$\gamma$ were selectively concentrated highly in pleural space than serum. Compared with malignant pleural effusion, IL-12 and IFN-$\gamma$ were significantly higher, but IL-10 were not in tuberculous pleural effusion. The results suggest that Th1 pathway contributes to immune resistant mechanism in tuberculous pleurisy. IFN-$\gamma$ and ADA revealed useful methods of differential diagnosis in tuberculous pleurisy from malignant pleural effusion.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.224-228
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• 2004

Background: The expression of BRG1 associated factors (BAF) 155 and BAF 170 in response to $IFN-{\gamma}$ or $TNF-{\alpha}$ was studied in astrocytoma cell lines and primary astrocytes. BAFs are complexed with BRG1 and are also associated with activated glucocorticoid for glucocorticoid trans-activation. Methods: $IFN-{\gamma}$ was pretreated for 18 hrs and cells were incubated with IL-1 or $TNF-{\alpha}$ for 72 hrs or 96 hrs with different concentrations of steroid. Cell death was measured by LDH assay. BAF expression was assayed by RT-PCR. Results: $IFN-{\gamma}$ increased cell death by dexamethasone in LN215 cells but not in LN319 cells. The $IFN-{\gamma}$ increased the expression of BAF 155 and BAF 170 in adult astrocytes and LN215 cells, but $IFN-{\gamma}$ decreased the expression of BAF 155/170 in LN319 cells. The effect of $IFN-{\gamma}$ on the expression of BAF was not as clear in fetal astrocytes as it was in adult astrocytes. Conclusion: Our results suggest cytokines produced during immune reaction or immunotherapy may modulate steroid susceptibility of astrocytes and astrocytoma cells by influencing the expression of BAFs.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.149-154
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• 2000

Background: Interleron-gamma(IFN-$\gamma$) and tumor necrosis factor-alpha(TNF-$\alpha$) playa critical role in protective immunity against Mycobacterium tuberculosis infection The change of IFN-$\gamma$ and TNF -$\alpha$ producing capacity in the course of antituberculous chemotherapy in patients with pulmonary tuberculosis was evaluated in this study. Method: In 29 patients with pulmonary tuberculosis, phytohemagglutinin(PHA) or purified protein derivative(PPD) stimulated production of IFN-$\gamma$ and TNF-$\alpha$ by peripheral blood mononuclear cells was quantified. Five patients were sampled before they underwent antituberculous treatment, 11 patients after 0-4 months, six after 4-completion and seven after treatment completion. Result: There was no difference in PHA- or PPD-stimulated production of IFN-$\gamma$ and TNF-$\alpha$ between each group. Conclusion: No difference in PHA- or PPD- stimulated production of IFN-$\gamma$ and TNF-$\alpha$ between two groups could be identified according to their treatment with pulmonary tuberculosis.

• Parasites, Hosts and Diseases
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• v.30 no.3
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• pp.219-226
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• 1992

This study was performed to observe the therapeutic effects of interferon-gamma ($IFN-{\gamma}$) and gamma-globulin (${\gamma}-globulin$) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxaBole(TMP-SMZ; 10~50 mg/mouse/day), mouse $IFN-{\gamma}(5{\times}10^4$ units/mouse/day) and mouse ${\gamma}-globulin$(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopatholo단ic and electron microscopic findings of the lungs, and number of p. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with $IFN-{\gamma}{\;}or{\;}{\gamma}-globulin$, and in the group of TMP- SMZ treatment(p<0.05), however, little effect was found in the group of T-globulin alone. Histopathologic 6ndings of p. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with $IFN-{\gamma}$. Treatment with either TMP-SMZ or $IFN-{\gamma}$ significantly reduced the number of cysts in the p. carinii pneumonia, but {\gamma}-globulin alone was ineffective. In electron microscopic findings of p. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or $IFN-{\gamma}$, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with $IFN-{\gamma}$ had synergistic effects in treatment of P carinii pneumonia in experi- mental mice.