• Clinical and Experimental Pediatrics
• /
• v.52 no.6
• /
• pp.667-673
• /
• 2009

Purpose : Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections. The purpose of this study was to analyze TLR2 surface expressions and TLR2-mediated tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6) production in patients with BCG vaccine-associated suppurative lymphadenitis. Methods : Peripheral monocytes were separated from 16 patients with BCG vaccine-associated suppurative lymphadenitis and 10 healthy controls using a magnet cell isolation kit. Monocytes ($1{\times}10^6$ cells/well) were incubated with a constant amount of $Pam_3CSK_4$ ($100{\mu}g/mL$) for 24 hours. TLR2 surface expression on monocytes was analyzed by FACS analysis and TLR-2 mRNA expression was determined by RT-PCR. TLR2-mediated $TNF-{\alpha}$ and IL-6 production were measured by ELISA. Results : In patients with BCG vaccine-associated suppurative lymphadenitis, low TLR2 expression on monocytes ($3.39{\pm}$1.2% versus $4.64{\pm}2.6%$) together with significantly lower TLR2 mRNA expression than in the healthy controls was seen after $Pam_3CSK_4$ stimulation. TLR2-mediated $TNF-{\alpha}$ and IL-6 production in patients with BCG vaccine-associated suppurative lymphadenitis ($TNF-{\alpha}$, $775.5{\pm}60.8pg/mL$; IL-6, $4,645.8{\pm}583.9pg/mL$) were also lesser than that in healthy controls ($TNF-{\alpha}$, $1,098.5{\pm}94.3pg/mL$; IL-6, $6,696.3{\pm}544.3pg/mL$). Conclusion : These findings suggest that low TLR2 expression on monocytes might be associated with increased susceptibility to BCG vaccine-associated suppurative lymphadenitis.

• Tuberculosis and Respiratory Diseases
• /
• v.39 no.1
• /
• pp.62-72
• /
• 1992

Background: T-cell mediated cellular immunity has been suggested as an important mechanism in mycobacterial infection and imbalance between helper/inducer and suppressor/cytotoxic T-cell has been suggested as an important immunological abnormality in the pathogenesis of tuberculosis in human. Method: To determine whether there is any difference in T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis, total numbers of WBC&lymphocytes were counted and helper/inducer and suppressor/cytotoxic cells were calculated by flow cytometry. Blastogenesis after stimulation with Concanavalin-A, Phytohemagglutinin and PPD were measured by $^3H$-thymidine uptake. PPD skin test was performed as an in vivo test. Results: 1)There was no significant difference in the size of PPD skin test between pulmonary and extrapulmonary tuberculosis groups. 2)Number of total lymphocytes significantly decreased in tuberculosis patients compared with healthy control group. But there was no significant difference between pulmonary and extrapulmonary tuberculosis groups. 3) Number of HLA-DR and Interleukin-2 receptor (+) cells were significantly increased in tuberculosis patients. But there was no significant difference between pulmonary and extra pulmonary tuberculosis groups. 4) There was no significant difference in the numbers of WBC, $T_3$, $T_4$ and $T_8$ lymphocytes and $T_4/T_8$ ratio between tuberculosis patients and healthy controls. 5) There was no significant difference in the blastogenesis after stimulation with specific and non-specific blastogens between tuberculosis patients and healthy controls. 6) The percentage and absolute number of $T_4$ lymphocyte were significantly correlated with the size of PPD skin test. (r=0.689 and 0.598). Conclusion: From these results, it is concluded that there was no difference in T-cell mediated immunity between pulmonary and extra pulmonary tuberculosis group. But, because it is suspected that there might be some difference in the role of T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis or even among the extrapulmonary tuberculosis patients, further studies would be required.

• Clinical and Experimental Pediatrics
• /
• v.52 no.5
• /
• pp.544-548
• /
• 2009

Purpose : To elucidate a potential association between Helicobacter pylori (HP) infection and iron-deficiency anemia (IDA) in infants and children in terms of the other factors related to iron utilization and storage although the association of ferritin was previously studied. Methods : We evaluated 135 infants (aged 6-24 months) admitted at Gyeongsang National University Hospital from 2000 to 2006. Western blot assays using the HP CagA antigen (120 kD) were conducted to identify infections. The concentrations of six parameters were measured: hemoglobin (Hb), serum ferritin, soluble serum transferrin receptors, interleukin-6, prohepcidin, and C-reactive protein. In addition, the infants were classified into IDA, anemia from inflammation (AI), unclassified anemia (UCA), and normal groups on the basis of Hb and ferritin concentrations. Results : In the IDA group (n=20), seven infants were infected with HP, with the other infants showing no evidence of infection. The mean Hb levels in the IDA group were significantly lower in HP-infected infants than those uninfected (7.1 vs. 8.2 g/dL, respectively); the mean ferritin levels were also significantly lower in the infected infants (3.2 vs. $6.8{\mu}g/L$). The other four parameters did not differ significantly among the IDA infants. No correlations were found between the six parameters and HP infection status in the other groups. Conclusion : There were no significant differences in the HP infection rates among the study groups. However, in the IDA group, the HP-infected infants had significantly lower serum ferritin and Hb levels than the HP-negative infants (P<0.05).

• Clinical and Experimental Pediatrics
• /
• v.48 no.2
• /
• pp.197-203
• /
• 2005

Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

• Korean Journal of Medicinal Crop Science
• /
• v.11 no.1
• /
• pp.5-12
• /
• 2003

The biological activities of extracts from Rubus coreanus Miq. were compared. About 70% of the growth of human hepatocarcinoma and 79% of human gastric cancer cell was inhibited in adding 1.0 mg/ml of the extracts of Rubus coreanus Miq. respectively. The growth of human breast cancer cells was also inhibited in adding 1.0 mg/ml of the extracts as well as 78% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 5, which is higher than those from the Rubus coreanus Miq. The growth of both human immune B and T cells was enhanced up to 1.4 to 1.8 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 78.8 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 70 pg/ml of interleukin-6(IL-6) from B cell. For screening regulate function of blood pressure, angiotensin converting enzyme(ACE) activity was inhibited up to 25% by adding the ethanol extract (1.0 mg/ml). In testing the hypoglycemic activity, 20% of ${\alpha}-glucosidase$ activity was inhibited for the extracts (0.5 mg/ml). GST activity was increased in the range of 1.2 to 1.6 times by adding extracts.

• IMMUNE NETWORK
• /
• v.1 no.2
• /
• pp.170-178
• /
• 2001

Background: Korean mistletoe (Viscum album) extract has been found to posses immunostimulatory activity. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to know whether this extract might activate mouse peritoneal macrophages to produce interleukin $1{\beta}$ (IL-$1{\beta}$). Methods: Hemagglutination assay was carried out to examine whether M11C contained a lectin or not. To know the effect of M11C on the production of IL-$1{\beta}$, the macrophages were treated by the M11C, and then collected the supernatant (M11C stimulated macrophages-conditioned media; MMCM). MMCM was analyzed for the IL-$1{\beta}$ quantification and mRNA expression by means of ELISA and RT-PCR, respectively. Results: Maximum effective dose and time of M11C on IL-$1{\beta}$ production from macrophages were $20{\mu}g/m{\ell}$ and 8 hours, respectively. This ELISA data was reconfirmed by immunoblotting assay. indicating that M11C is a good candidate for an immunomodulator. The dose and time dependent effects of M11C on the expression of IL-$1{\beta}$ mRNA from macrophages was also shown in expression of mRNA detected by RT-PCR. Treatment dose and time for the maximum expression of IL-$1{\beta}$ mRNA were $20{\mu}g/m{\ell}$ and 4 hours, respectively. Maximum gene expression of IL-$1{\beta}$ was much earlier than maximum production of it. Conclusion: As results, Korean mistletoe extract, M11C, may be used for an immunomodulator. This will be able to make up for and solve the problems caused by existent immunoagent with many adverse effects through many other studies in future including one molecule extraction.

• IMMUNE NETWORK
• /
• v.8 no.1
• /
• pp.29-37
• /
• 2008

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.

• Asian-Australasian Journal of Animal Sciences
• /
• v.30 no.8
• /
• pp.1190-1197
• /
• 2017

Objective: Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods: An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha ($TNF-{\alpha}$), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce's correlation analysis. Results: Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and $TNF-{\alpha}$ showed no difference, while the values of $TNF-{\alpha}$ in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion: AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

• Journal of Periodontal and Implant Science
• /
• v.37 no.3
• /
• pp.563-573
• /
• 2007

Genetic polymorphisms associated with aggressive periodontitis have previously been reported. Interleukin-10 is an immunoregulatory cytokine that plays a role in the pathogenesis of periodontitis. Individual capacity for IL-10 production appears to be under genetic influence, The aim of present investigation was to explore possible genetic association of IL-10 gene promoter polymorphisms with generalized aggressive periodontitis. The study population consisted of 37 generalized aggressive periodontitis patients from the Department of Periodontology, Chonnam National University Hospital and 27 control subjects, all the subjects were non-smokers, Genomic DNA was obtained from buccal swab. The IL-10promoter -597, -824, -1082 positions were genotyped by amplifying the polymorphic regions using polymerase chain reaction (PCR) , followed by restriction enzyme digestion and gel electrophoresis. IL-10-597 C (allele 1) to A (allele 2) and IL-10-824 C (allele 1) to T (allele 2) and IL-10-1082 G (allele 1) to A (allele 2) polymorphisms were examined. The results were as follows. 1. In patients, the distribution of genotypes C/C, C/A and NA at Il-10-597 was determined to be 13.5%, 37.8% and 48.7%, respectively and the distribution of genotypes at IL-10-824 was the same as that of IL-10-597. The distribution of genotypes G/G, G/A and NA at IL-10-1082 was found to be 2.7%, 16.2% and 81. 4%, respectively. No statistical difference in genotype distribution was found between the patient and control groups. 2. Allele 2 carriage rate at the three position of the IL-10 promoter region was higher in the control group than the patient group. 3. Allele 2 frequencies at IL-10-597 and -824 positions were higher in female group than male group and its difference was statistically significant(p<0.05). No significant difference in genotype distribution between the control and patient groups. Allele frequency between control and patient groups was not significantly different although allele 2 frequency at the three positions in the IL-10 promoter region appeared to be higher in control group. In conclusion, no clear association between IL-10 gene promoter polymorphisms and generalized aggressive periodontitis in Korean was observed.

• Journal of Pharmacopuncture
• /
• v.20 no.2
• /
• pp.127-131
• /
• 2017

Objectives: Polymorphonuclear neutrophils (PMNs) constitute the first line of defense against invading microbial pathogens. Early events in inflammation involve the recruitment of neutrophils to the site of injury or damage where changes in intracellular calcium can cause the activation of pro-inflammatory mediators from neutrophils including superoxide generation, degranulation and release of myeloperoxidase (MPO), productions of interleukin (IL)-8 and tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), and adhesion to the vascular endothelium. To address the anti-inflammatory role of flavonoids, in the present study, we investigated the effects of the flavonoids quercetin and vitexin on the stimulus-induced nitric oxide (NO), $TNF-{\alpha}$, and MPO productions in human neutrophils. Methods: Human peripheral blood neutrophils were isolated, and their viabilities were determined by using the Trypan Blue exclusion test. The polymorphonuclear leukocyte (PMNL) preparations contained more than 98% neutrophils as determined by morphological examination with Giemsa staining. The viabilities of cultured neutrophils with various concentrations of quercetin and vitexin ($1-100{\mu}M$) were studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without quercetin and vitexin ($25{\mu}M$) for 45 min, and stimulated with phorbol 12-myristate 13-acetate (PMA) ($10^{-7}M$). NO production was carried out through nitrite determination by using the Griess method. Also, the $TNF-{\alpha}$ and the MPO productions were measured using enzyme-linked immunosorbent assay (ELISA) kits and MPO assay kits. Results: Neutrophil viability was not affected up to a concentration of $100{\mu}M$ of quercetin or vitexin. Both quercetin and vitexin significantly inhibited $TNF-{\alpha}$, NO, and MPO productions in human neutrophils (P < 0.001). Conclusion:The present study showed that both quercetin and vitexin had significant anti-inflammatory effects. Thus, treatment with either quercetin or vitexin may be considered as a therapeutic strategy for treating patients with neutrophil-mediated inflammatory diseases.