• Preventive Nutrition and Food Science
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• v.13 no.4
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• pp.354-361
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• 2008

A novel bacterium isolated from Cheonggukjang was identified as a glutamate-dependent Bacillus subtilis HA with 98.3% similarity to Bacillus subtilis Z99104. Optimization of poly-$\gamma$-glutamic acid ($\gamma$-PGA) production by modulating fermentation factors including carbon sources, nitrogen sources, inorganic salts and fermentation time was investigated. Optimum culture broth for $\gamma$-PGA production consisted of 3% glutamate, 3% glucose and various salts, resulting in the PGA production of 22.5 g/L by shaking culture for 72 hr at $37^{\circ}C$. Average molecular weight of $\gamma$-PGA was determined to be 1,220 kDa through MALLS analysis. The $\gamma$-PGA solution showed a typical pseudoplastic flow behavior, and a great decrease in consistency below pH 6.0 regardless of the same molecular weight of $\gamma$-PGA. The molecular weights of isolated $\gamma$-PGA were drastically decreased by heat treatment in various acidic conditions, resulting in different hydrolysis of $\gamma$-PGA. The consistency of $\gamma$-PGA solution was greatly decreased with increase heating time in acidic conditions.

• Biomedical Science Letters
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• v.15 no.3
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• pp.179-185
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• 2009

In our previous report, we showed that $PPAR{\gamma}$ does not influence adipogenesis in females with functioning ovaries, indicating that $PPAR{\gamma}$ activity on adipogenesis is associated with sex-related factors. Among the sex-related factors, estrogen has been recognized as a major factor in inhibiting adiposgenesis in females. Thus, we hypothensized that $17{\beta}$-estradiol (E) inhibits 3T3-L1 cell adipogenesis by preventing $PPAR{\gamma}$ activity. E decreased triglyceirde accumulation in differentiated 3T3-L1 cells compared with control group. E also decreased the expression of $PPAR{\gamma}$ mRNA as well as $PPAR{\gamma}$ dependent adipocyte-specific genes, such as adipocyte fatty acid binding protein and tumor necrosis factor $\alpha$. In addition, E not only decreased luciferase reporter activity by $PPAR{\gamma}$, but also transfection of estrogen receptor $\alpha$ ($ER{\alpha}$) or $ER{\beta}$ led to decreases in $PPAR{\gamma}$ reporter gene activation. Moreover, E-activated ERs significantly decreased the luciferase reporter gene activation induced by $PPAR{\gamma}$ transfection, suggesting that estrogen-activated ERs inhibit $PPAR{\gamma}$-dependent transactivation. Accordingly, our results demonstrate that E inhibits the action of $PPAR{\gamma}$ on adipogenesis through E activated ER, providing evidence that lack of estrogen may potentiate $PPAR{\gamma}$ action on adipogenesis.

• Journal of the Korean Mathematical Society
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• v.53 no.5
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• pp.1167-1182
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• 2016

Let M be an R-module, where R is a commutative ring with identity 1 and let G(V,E) be a graph. In this paper, we study the graphs associated with modules over commutative rings. We associate three simple graphs $ann_f({\Gamma}(M_R))$, $ann_s({\Gamma}(M_R))$ and $ann_t({\Gamma}(M_R))$ to M called full annihilating, semi-annihilating and star-annihilating graph. When M is finite over R, we investigate metric dimensions in $ann_f({\Gamma}(M_R))$, $ann_s({\Gamma}(M_R))$ and $ann_t({\Gamma}(M_R))$. We show that M over R is finite if and only if the metric dimension of the graph $ann_f({\Gamma}(M_R))$ is finite. We further show that the graphs $ann_f({\Gamma}(M_R))$, $ann_s({\Gamma}(M_R))$ and $ann_t({\Gamma}(M_R))$ are empty if and only if M is a prime-multiplication-like R-module. We investigate the case when M is a free R-module, where R is an integral domain and show that the graphs $ann_f({\Gamma}(M_R))$, $ann_s({\Gamma}(M_R))$ and $ann_t({\Gamma}(M_R))$ are empty if and only if $$M{\sim_=}R$$. Finally, we characterize all the non-simple weakly virtually divisible modules M for which Ann(M) is a prime ideal and Soc(M) = 0.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1399-1405
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• 2013

The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.

• BMB Reports
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• v.33 no.2
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• pp.97-102
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• 2000

Phosphoinositide-specific phospholipase C-${\gamma}1$ (PLC-${\gamma}1$) is a pivotal mediator in the signal transduction cascades induced by many growth factors. Using a yeast two-hybrid system, heat-shock protein 90 (Hsp90) was identified as a PLC-${\gamma}1$-binding protein. A co-immunoprecipitation experiment, using anti-PLC-${\gamma}1$ antibody, demonstrated an in vivo interaction between Hsp90 and PLC-${\gamma}1$ in the NIH-3T3 cells. The interaction in NIH-3T3 was unaffected by the PDGF treatment, inducing phosphorylation and activation of PLC-${\gamma}1$. Direct interaction between Hsp90 and PLC-${\gamma}1$ was confirmed by in vitro binding experiments using purified Hsp90 and PLC-${\gamma}1$. Furthermore, Hsp90 increased the $PIP_2$-hydrolyzing activity of PLC-${\gamma}1$ up to 2-fold at $0.1{\mu}M$ in vitro. Taken together, we show for the first time, the interaction of PLC-${\gamma}1$ with Hsp90, both in vivo and in vitro. We suggest that Hsp90 may play a role in PLC-${\gamma}1$-mediated signal transduction.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7995-8001
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• 2014

Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.

• IMMUNE NETWORK
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• v.2 no.1
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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.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.36-44
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• 1998

Background: IFN-$\gamma$ is known to activate mononuclear phagocytes and to mediate host defense mechanism against some intracellular microorganisms, but little is known about anti-mycobacterial activity and mechanism of IFN-$\gamma$ in human. In this study, we investigated the role of IFN-$\gamma$ in the pathogenesis of tuberculosis by observing the effect of IFN-$\gamma$ on the phagocytosis of M.tuberculosis(MTB) and on the production of TNF-$\alpha$ by human pulmonary alveolar macrophage. Method: Pulmonary alveolar macrophage(PAM) were prepared with adhesion purification method from bronchoalveolar lavage fluid obtained from 8 persorn without active lung lesion and cultured($1{\times}10^6cells/ml$) with MTB($3{\times}10^7$ bacteria/ml) with or without IFN-$\gamma$(300U/ml), LPS(0.5ug/ml) and autologous serum(10%). After 2 hours, the percentage of PAM-phagocytosed MTB was counted after AFB staining(modified Kynion method). TNF-$\alpha$ production by PAM stimulated by IFN-$\gamma$(300U/ml), MTB($1{\times}10^6bacteria/ml$) and LPS(0.5ug/ml) for 24hours was measured in culture supernatant using ELISA method. The degree of phagocytosis of MTB by PAM stimulated with IFN-$\gamma$(300U/ml) and LPS(0.5ug/ml) for 24hours was also investigated. Results: IFN-$\gamma$ did not influence the phagocytosis of MTB by PAM(percentage of PAM-phagocytosed MTB: control: $22.1{\pm}4.9$, IFN-$\gamma$: $20.3{\pm}5.3$) and did not increase TNF-$\alpha$ production by PAM (control: $21{\pm}38pg/ml$, IFN-$\gamma$: $87{\pm}106pg/ml$), and the degree of phagocytosis of MTB by PAM pre-stimulated with IFN-$\gamma$ for 24 hours, was not increased (control: $24.5{\pm}9.5$, IFN-$\gamma$: $23.4{\pm}10.1$). Conclusion: IFN-$\gamma$ does not influence on the phagocytosis of MTB and TNF-$\alpha$ production by PAM.

• KSBB Journal
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• v.21 no.3
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• pp.204-211
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• 2006

For the production of the recombinant human interferon-gamma(rhIFN-${\gamma}$) in Escherichia coli, human glucagon and ferritin heavy chain were used as fusion partners. Even though rhIFN-${\gamma}$ is expressed as an inclusion body form in E. coli because of strong hydrophobicity of itself, over 50% of fused rhIFN-${\gamma}$ was expressed as soluble form in E. coli $Origami^{TM}$(DE3) harboring pT7FH(HE)-IFN-${\gamma}$ which encodes ferritin heavy chain-fused rhIFN-${\gamma}$. In the case of using glucagon-ferritin heavy chain hybrid mutant as a fusion partner, 6X His-tag was additionally introduced to N-terminus of GFHM(HE)-IFN-${\gamma}$ for enhancing purification yields of rhIFN-${\gamma}$. Fusion protein HGFHM(HE)-IFN-${\gamma}$ with two 6X His-tag was more effectively bound to Ni-NTA agarose bead than GFHM(HE)-IFN-${\gamma}$ with a 6X His-tag. rhIFN-${\gamma}$ was completely purified from enterokinase-treated HGFHM(HE)-IFN-${\gamma}$ by Ni-NTA affinity column. For high-level production of rhIFN-${\gamma}$, glucose was used as the sole carbon source with simple exponential feeding rate($2.4{\sim}7.2g/h$) in fed-batch process. The effective lactose concentration for the expression of the rhIFN-${\gamma}$ was $10{\sim}20mM$. Under the fed-batch culture conditions, rhIFN-${\gamma}$ production yield reached 11 g DCW/L for 6 hours after lactose induction.