• Korean Journal of Food Science and Technology
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• v.46 no.4
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• pp.516-521
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• 2014

The mechanisms underlying the refractory effects of flutamide, a first-line oral anti-androgen drug, have not been entirely elucidated. In the present study, we investigated the mechanism of flutamide-induced hormone-refractory prostate cancer cell growth and its modulation by resveratrol, a phytoalexin present in grapes. Resveratrol significantly attenuated interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) transcriptional activity and dihydrotestosterone (DHT) or IL-6-induced prostate-specific antigen (PSA) transcriptional activity. Furthermore, compared to treatment with DHT or IL-6 alone, combination treatment of cells significantly increased PSA transcriptional activity, and resveratrol markedly diminished DHT plus IL-6-induced STAT3 and PSA transcriptional activities. Thus, the inhibitory effects of resveratrol on IL-6-, DHT-, and flutamide-induced hormone-refractory prostate cancer cell growth are partly mediated by the suppression of STAT3 reporter gene activity, suggesting that resveratrol represents a promising therapy for prostate cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.945-953
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• 1996

Background : Many acute and chronic lung diseases including pneumoconiosis are characterized by the presence of increased numbers of activated macrophages. These macrophages generate several inflammatory cell chemoattractants, by which neutrophil migrate from vascular compartment to the alveolar space. Recruited neutrophils secrete toxic oxygen radicals or proteolytic enzymes and induce inflammatory response. Continuing inflammatory response results in alteration of the pulmonary structure and irreversible fibrosis. Recently, a polypeptide with specific neutrophil chemotactic activity, interleukin-8(IL-8), has been cloned and isolated from a number of cells including : monocytes, macrophages and fibroblasts. IL-1 and/or TNF-${\alpha}$ preceded for the synthesis of IL-8, and we already observed high level of IL-1 and TNF-${\alpha}$ in the pneumoconioses. So we hypothesized that IL-8 may be a central role in the pathogenesis of pneumoconiosis. In order to evaluate the clinical utility of IL-8 as a biomarker in the early diagnosis of pneumoconiosis, we investigated the increase of IL-8 in the pneumoconiotic patient and the correlation between IL-8 level and progression of pneumoconiosis. Method : We measured IL-8 in the serum of 48 patients with pneumoconiosis and 16 persons without dust exposure history as a control group. Pneumoconiotic cases were divided into 3 groups according to ILO Classification : suspicious group(n=16), small opacity group(n=16) and large opacity group(n=16). IL-8 was measured by a sandwich enzytne immunoassay technique. All data were expressed as the $mean{\pm}standard$ deviation. Results: 1) The mean value of age was higher in the small opacity and large opacity group than comparison group, but smoking history was even. Duration of dust exposure was not different among 3 pneumoconiosis groups. 2) IL-8 level was $70.50{\pm}53.63pg/m{\ell}$ in the suspicious group, $107.50{\pm}45.88pg/m{\ell}$ in the small opacity group, $132.50{\pm}73.47pg/m{\ell}$ in the large opacity group and $17.85{\pm}33.85pg/m{\ell}$ in the comparison group. IL-8 concentration in all pneumoconiosis group was significant higher than that in the comparison group(p<0.001). 3) IL-8 level tended to increase with the progression of pneumoconiosis. Multiple comparison test using Anova/Scheffe analysis showed a significant difference between suspicious group and large opacity group(p<0.05). 4) The level of IL-8 was correlated with the progression of pneumoconiosis(r=0.4199, p<0.05). Conclusion : IL-8 is thought to be a good biomarker for the early diagnosis of pneumoconiosis.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.25 no.3
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• pp.1-12
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• 2012

Objectives : Fagopyrum esculentum(FE) has been used for removal of inflammation of internal organs and treatment of sore and ulcer by heat toxin in Korean herbal medicines. In this study, To investigated the protective effect of FE on allergic response, we determined whether FE inhibits allergic response. Methods : The effect of FE was analyzed by ELISA, RT-PCR and Western blot in RBL-2H3 cells. We investigated cell viability, ${\beta}$-hexosaminidase, as a marker of degranulation, cytokne, and intracellular ROS and MAPK and NF-${\kappa}B$ signaling. Results : We found that FE suppressed ${\beta}$-hexosaminidase release, the production of IL-4 and TNF-${\alpha}$ and intracellular ROS level in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. FE also significantly inhibited cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF in RBL-2H3. In addition, PF suppressed the phospholyation of ERK1/2, JNK1/2, p38 and $I{\kappa}B{\alpha}$ and NF-${\kappa}B$ signal transduction pathway. Conclusions : Our results indicate that FE protects against allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and production of cytokines and ROS via the suppression MAPK and NF-${\kappa}B$ of signal transduction. Abbrevations : FE, Fagopyrum esculentum; RBL-2H3, rat basophilic leukemia cell line; ROS, reactive oxygen species; MAPK, Mitogen-activated protein kinase; $NF{\kappa}B$, nuclear factor ${\kappa}B$; $TNF{\alpha}$, Tumor necrosis factor alpha; GM-CSF, Granulocyte macrophage colony-stimulating factor; ERK, extracellular-signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; p38, p38 MAP kinase; $I{\kappa}B{\alpha}$, inhibitory-kappa B alpha.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.

• The korean journal of orthodontics
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• v.30 no.6 s.83
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• pp.713-721
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• 2000

Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

• Restorative Dentistry and Endodontics
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• v.31 no.3
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• pp.153-160
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• 2006

We investigated the secretion of Interleukin-8 (IL-8) from ginviva and periodontal ligament stimulated with Substance P (SP) and Calcitonin Gene-related Peptide (CGRP). Gingiva (GF), periodontal ligament (PDLF) and pu)p (PF) tissues were collected from extracted intact 3rd molars. Cultured cells were stimulated with different concentrations of SP for 4 hrs, and stimulated with SP, CGRP and Tumor Necrosis Factor-$\alpha$ (TNF-$\alpha$) for 8 hrs. Then RNase Protection Assay was carried out. ELISA was performed using supernatants of stimulated cells for quantitative analysis of IL-8. Results were assessed using student t-test with significance of P<0.05. According to this study, the results were as follows: 1. IL-8 mRNA was detected in all type of cells studied (PF, GF and PDLF) 2. IL-8 mRNA expression was not increased after stimulating 4 hrs with SP ($10^{-5}M$) and SP ($10^{-8}M$) compared with Mock stimulation in all type of cells studied. 3. IL-8 mRNA expression was not increased after stimulating 8 hrs with SP ($10^{-4}M$) and CGRP ($10^{-6}M$) compared with Mock stimulation in all type or cells studied. 4. TNF-$\alpha$ (2 ng/ml) increased the expression of IL-8 mRNA in all kind of cells studied. 5. The secretion of IL-8 from GF was increased 8 hrs after the stimulation with CGRP ($10^{-6}M$)(p<0.05). 6. The secretion of IL-8 from PDLF was. increased 8 hrs after the stimulation with SP ($10^{-4}M$)(p<0.05). Calcitonin Gene-related Peptide (CGRP) increased Interleukin-8 (IL-8) which plays an important role in chemotaxis of neutrophil in Calcitonin Gene-related Peptide (CGRP) gingival tissue , whereas Substance P increased the secretion of IL-8 from periodontal ligament.

• Preventive Nutrition and Food Science
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• v.3 no.3
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• pp.282-286
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• 1998

To determine the immune effect of kimchi extracts in mice, 0.5mg/day of the extracts from kimchis, which were prepared with conventionally (general kimchi)and organically(organic kimchi) cultivated ingredients, were treated orally to male BALB/c mice. Following 1, 3 and 5 weeks of treatment , the Interleukin-2(IL-2) production in the presence (con-A-stimulated )or the absence(spontaneous)of con A 95 $\mu\textrm{g}$/ml) and the natural killer cell (NK) activity of the splenocytes were measured. The IL-2 production in most of treatments with methanol extract from general kimchi were significantly higher than those of control(p<0.05).And at the 3 weeks of treatment, the spontaneous or con A-stimulated IL-2 productions from splenocytes of mice treated with it increased more than those of control group, by 2.8 and 2.2 times, respectively. However, the longer the treatment with methanol extracts from organic kimchi showed the higher the enhancing effect on the IL-2 production. The spontaneous or con A-stimulatdIL-2 productions form splenocytes of mice treated with dicholoromethyane fraction from general kimchi also increased at 5 weeks of treatment compared to those of control group, by 2.7 and 2.5 times, respectively. The natural killer cell activity of splenocytes from mice treated with methano lextracts from general kimchi for 1 ~5 weeks significantly higher than that of control goup (p<0.01). The effect of methano extracts from general kimchi was the highest at 3 weeks of treatment, as same as in the IL-2 production. The enhancing effect of methano extracts from organic kimchi on the NK cell activity was the highest at 5 weeks of treatment . The NK cell activity of splenocytes from mice treated with dichloromethane fraction from general kimchi for 5 weeks was significantly higher than those in control and 3 weeks of treatment. These results showed that the effects of kimchi extracts on the IL-2 production and the NK cell activity in mice were profound in long term of treatment (3 and 5 weeks than 1 week) . We suggest that kimchi extracts might have an immune effect in part due to its enhancing action on the IL-2 production and the NK cell activity.

• Bulletin of the Korean Chemical Society
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• v.22 no.11
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• pp.1280-1282
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• 2001

• 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.

• The Korean Journal of Food And Nutrition
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• v.25 no.2
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• pp.362-367
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• 2012

Corn has been used for a long time as a traditional remedy, as well as a food source. We previously reported that in vitro supplementation of corn water extracts enhanced the proliferation of splenocytes, compared to the control group. In this study, we examined the immunomodulative effect of a water extract of corn. Seven to eight weeks old mice(Balb/c) were fed an ad libitum chow diet, and were orally administrated a water extract of corn every other day, for four weeks, at two different concentrations(50 and 500 mg/kg B.W). Cytokine production(IL-2, IL-10 and IFN-${\gamma}$) by macrophages stimulated with LPS or not stimulated with LPS was detected by ELISA assay using the cytokine kit. In an ex vivo study, the cytokines IL-2, IL-10 and IFN-${\gamma}$ were detected at 500 mg/kg b.w. supplementation group with LPS stimulation in all cases. Also, the ratio of IFN-${\gamma}$ to IL-10 was in the range of 0~3 with mitogen stimulation, such as con A and LPS. In conclusion, this study suggests that in mice, corn extracts may enhance immune function by regulating the cytokine production(IL-2, IL-10 and IFN-${\gamma}$) of the activated macrophages.