• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.464-470
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• 2000

Background : The recognition of bronchial asthma as an inflammatory disease led to the search for soluble markers that would be useful in assessing airway inflammation. Interleukin-6 (IL-6) is a representative proinflammatory cytokine that has been shown to be connected with various inflammatory diseases. IL-6 acts via specific receptors that consist of the IL-6 binding glycoprotein gp80 and the signal transducer gp130. In the search for markers of airway inflammation, delete the role of soluble interleukin-6 receptor (sIL-6R) and IL-6 in acute asthma were investigated. Methods : Serum levels of sIL-6R and IL-6 were measured in 78 acute asthmatics, in 15 patients with asymptomatic asthma and in 10 healthy control subjects by a specific ELISA using a murine antihuman IL-6R, IL-6 mAb ($Quantikine^{(R)}sIL$-6R, IL-6). Results : Serum levels of IL-6 in acute asthmatics significantly exceeded those of control subjects. The levels of sIL-6R in acute asthmatics were also significantly increased compared to those of control subjects. The serum concentrations of IL-6 obtained in acute asthmatics were elevated compared with those in asymptomatic asthmatics. However, association between eosinophilic count/IgE and IL-6/sIL-6R in acute asthma could not be found. Conclusion : Our results suggest that IL-6 may be involved in the pathogenesis of acute asthma, and serum levels of IL-6 and sIL-6R may reflect the severity of airway inflammation.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.27-34
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• 1999

Purpose: This study was designed to investigate the changes in soluble interleukin-2 receptor (sIL-2R) level in sera and urines of children with primary nephrotic syndrome, eliminating the confounding effects of age, proteinuria, and steroid treatment. Methods: Soluble IL-2R was measured by ELISA in sera and urines from patients with minimal change nephrotic syndrome or focal segmental glomerulosclerosis as well as from healthy controls. The serum levels and urinary sIL-2R/creatinine ratios were compared between control group and the 12 patient groups divided by their ages (0-1, 2-4, over 5 years), and presence or absence of proteinuria and/or steroid treatment (PU+Tx-, PU+Tx+, PU-Tx+, PU-Tx-). Results: Though the differences were not statistically significant probably because of the small numbers, serum sIL-2R levels seemed to be higher in younger age groups both in patients and control group. Nephrotic children did not show higher serum levels than normal children. Among the patients, proteinuric condition seemed to raise and steroid treatment tended to suppress the serum sIL-2R levels. Urinary sIL-2R/creatinine ratios were higher in younger age groups, more significantly in patients (P<0.001). Proteinuria and steroid treatment affected the urinary sIL-2R/creatinine ratios by the same way as the serum sIL-2R levels. Serum sIL-2R levels and urinary sIL-2R/creatinine ratios were not different between groups of different histologic findings or steroid responsiveness (P>0.05). Conclusion: Serum sIL-2R levels and the urinary sIL-2R/creatinine ratios were higher in younger age, and they were not higher in nephrotic patients compared to control group. The patients in relapse showed higher levels, while the levels were suppressed with steroid treatment. In proteinuric state, urinary sIL-2R/creatinine ratios reflected serum sIL-2R levels.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.135-143
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• 1994

Background: The cell mediated immunity has an important role in the pathogenesis of tuberculosis. sIL-2R has been known as a sensitive marker of T lymphocyte activation Elevated serum levels of sIL-2R have been found in patients with lymphoproliferative disorders, organ transplantation, autoimmune diseases, and various granulomatous diseases. Elevated levels of sIL-2R have been also found in the serum and pleural fluid of the patients with tuberculosis. To evaluate the diagnostic value of sIL-2R in the differentiation of tuberculous pleurisy and nontuberculous pleurisy. We measured the level of sIL-2R in the sera and pleural fluids of 12 patients with tuberculous pleurisy and 32 patients with nontuberculous pleurisy. Method: Samples of pleural fluid and serum were centrifuged at 2500 rpm for 10 min to remove cell pellets. Soluble IL-2R was measured with a sandwitch enzyme immunoassay using the Cellfree(r) Interleukin-2 Receptor Test kit(T-cell science,Inc. Cambridge, MA). Results: The results obtained were as follows: 1) The sIL-2R level in pleural fluid of the patients with tuberculous pleurisy was higher than that of patients with nontuberculous pleurisy(P<0.005). 2) When the sIL-2R level above 5,000 u/ml in pleural fluid was used as the cut-off value to diagnose tuberculous pleurisy, it had a sensitivity of 84.6% and a specificity of 90.9%. 3) The sIL-2R level in the sera of the patients with tuberculous pleurisy was higher than that of patients with bacterial pleural effusions and normal control group(P<0.05) and there was no difference of levels compared with malignant pleural effusions and transudative pleural effusions(P>0.05). 4) In patients with tuberculous pleurisy, the mean concentration of sIL-2R in pleural fluid was higher than that in serum(P<0.005). Conclusion: These findings suggest that the measurement of elevated levels of pleural fluid sIL-2R in tuberculous pleurisy may be useful in the differential diagnosis between patients with tuberculous pleurisy and nontuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• BMB Reports
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• v.52 no.3
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• pp.214-219
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• 2019

The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.87-99
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• 2004

This experiment was designed to investigate the effect of Coptis japonica Makino(CJM) on the Alzheimer's disease. The effects of CJM extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins (APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit rats induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. CJM extract suppressed $IL-1{\beta}$, IL-6 mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 2. CJM extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 3. CJM extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 4. CJM extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. 5. CJM extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. According to the above results, it is suggested that CJM extract might be usefully applied for prevention and treatment of Alzheimer's disease and memory deficit symptom.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.130-138
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• 2005

This experiment was designed to investigate the effect of Phellodendron amurense(PLDA) on the Alzheimer's disease. The effects of PLDA extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. PLDA extract suppressed $IL-1{\beta}$, IL-6, APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ ; AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$. PLDA extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. PLDA extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that PLDA extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Tuberculosis and Respiratory Diseases
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• v.55 no.3
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• pp.250-256
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• 2003

Background : Anthracofibrosis, a descriptive term for multiple black pigmentation with fibrosis on bronchoscopic examination, has a close relationship with active tuberculosis (TB). However, TB activity is determined in the later stage by the TB culture results in some cases of anthracofibrosis. Therefore, it is necessary to identify early markers of TB activity in anthracofibrosis. There have been several reports investigating the serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody for the evaluation of TB activity. In the present study, we tried to measure the above mentioned serologic markers for the evaluation of TB activity in patients with anthracofibrosis. Methods : Anthracofibrosis was defined when there was deep pigmentation (in more than two lobar bronchi) and fibrotic stenosis of the bronchi on bronchoscopic examination. The serum of patients with anthracofibrosis was collected and stored under refrigeration before the start of anti-TB medication. The serum of healthy volunteers (N=16), patients with active TB prior to (N=22), and after (N=13), 6 month-medication was also collected and stored. Serum IL-2 $sR{\alpha}$, IFN-${\gamma}$ were measured with ELISA kit (R&D system, USA) and serum TBGL antibody was measured with TBGL EIA kit (Kyowa Inc, Japan). Results : Serum levels of IL-2 $sR{\alpha}$ in healthy volunteers, active TB patients before and after medication, and patients with anthracofibrosis were $640{\pm}174$, $1,611{\pm}2,423$, $953{\pm}562$, and $863{\pm}401$ pg/ml, respectively. The Serum IFN-${\gamma}$ levels were 0, $8.16{\pm}17.34$, $0.70{\pm}2.53$, and $2.33{\pm}6.67$ pg/ml, and TBGL antibody levels were $0.83{\pm}0.80$, $5.91{\pm}6.71$, $6.86{\pm}6.85$, and $3.22{\pm}2.59$ U/ml, respectively. The serum level of TBGL antibody was lower than of other groups (p<0.05). There was no significant difference of serum IL-2 $sR{\alpha}$ and IFN-${\gamma}$ levels among the four groups. Conclusion : The serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody were not useful in the evaluation of TB activity in patients with anthracofibrosis. More useful ways need to be developed for the differentiation of active TB in patients with anthracofibrosis.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.435-440
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• 2009

Purpose : The concentration of soluble transferrin receptor (sTfR) is estimated as an iron parameter to evaluate erythropoiesis and iron status. The aim of our study is to evaluate the correlation between sTfR concentration and inflammatory parameters and to distinguish iron deficiency anemia from anemia of inflammation. Methods : One hundred and forty-four infants younger than two years of age who visited Gyeongsang University Hospital for 7 years from 2000 to 2006 were enrolled. Patients who had hemoglobin (Hb) <11 g/dL and ferritin <12 mg/L were excluded. Routine hematologic lab, serum ferritin, sTfR, and inflammatory markers [C-reactive protein(CRP), interleukin-6(IL-6), and absolute neutrophil count (ANC)] were investigated. Results : In all patients, the sTfR concentration showed a correlation with Hb, ferritin, MCV, and ANC, but not with CRP and IL-6. In multiple regression models, positive correlations were found between sTfR concentration and IL-6 (r=0.078, P=0.043), and negative correlations were found between sTfR concentration and ANC (r=-0.117, P=0.033) and MCV (r=-0.027, P=0.009). Conclusion : sTfR concentration was influenced by inflammatory parameters. Therefore, sTfR does not appear to be a useful parameter for discriminating between iron deficiency anemia and anemia of inflammation in infants.

• 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.