• Journal of Periodontal and Implant Science
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• v.26 no.3
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• pp.641-654
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• 1996

In infectious disease, invasion of host tissue by bacteria or their products frequently induces a wide variety of inflammatory and immunopathologic reaction. Evidence indicates that cytokines are involved in the initiation and progression of chronic inflammatory diseases, such as periodontitis. Interleukin-6, which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. Periodontal diseases are characterized by chronic inflammation of the periodontium with alveolar bone resoption. A principal driving force behind this response appears to lie in the immune system's response to bacteria. Many of the cell components which have been shown to function as virulence factors in gram-negative bacteria are associated with the bacterial surface. Of these, lipopolysaccharide has been characterized as one that mediates a number of biological activities which can lead to the destruction of host tissue. Non-steroidal antiinflammatory drug is used for reduce inflammation, and most of NSAIDs inhibit prostaglandine $E_2$ production, but it is shown that $PGE_2$ production is stimulated by IL-1 in recent study. So, the influence of other cytokines except $PGE_2$ on periodontium can not be avoided. Therefore, new antiinflammatory drug is needed. Rhizoma coptidis is used in oriental medicine for anti-inflammation and antiseptics. In this present study, we examined the IL-6 release in periodontal ligament cells treated with the lipopolysaccharide, and also the effect of rhizoma coptidis on cellular activity and IL-6 production of periodontal ligament cells. To evaluate the effect of rhizoma coptidis on cellular activity, the cells were seeded at a cell density of $1{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 1-6, 10-9 and 10-12 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 1 and 2 days, respectively. Then, MTT assay were carried out. To evaluate the effect of rhizoma coptidis on IL-6 production, the cells were seeded at a cell density of $1.5{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 10-9 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 3, 6, 12 and 24 hours. Then, amounts of IL-6 production is measured by IL-6 ELISA kit used. The results were as follows : 1. Rhizoma coptidisrbelow to ($10^{-6}g/ml$) significantly increaed cellular activity of periodontal ligament cells than control. 2. Rhizoma coptidist ($10^{-9}g/ml$) significantly increased cellular activity of LPS($5{\mu}g/ml$)-treated periodontal ligament cells than control. 3. LPS(5 and $10{\mu}g/ml$) significantly increased IL-6 production of periodontal ligament cells than control. 4. Rhizoma coptidis($10^{-9}g/ml$) decreased IL-6 production of LPS ($5{\mu}g/ml$)-treated periodontal.ligarnent cells than LPS only tested group. These findings suggest that stimulation of the IL-6 release of periodontal ligament cells by LPS may have a role in the progression of inflammation and alveolar bone resoption in periodontal disease, and that inhibition of the IL-6 release of cells and stimulation of cellular activity by rhizoma coptidis may help the periodontal regeneration.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.257-263
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• 2013

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7869-7873
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• 2014

Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, are immunomodulatory products that play important roles in responses in cancers and inflammation. We tested the association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the risk of bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association of these SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotype distributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, among patients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancer was significant. After a control adjustment for age and sex, the following results were recorded: CC genotype (OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+CC (OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygous genotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13, 95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover among high risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 beta heterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86, p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggests that IL-12(3'UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk of bladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.

• Food Science and Preservation
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• v.24 no.8
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• pp.1158-1167
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• 2017

In this study, ${\beta}$-1,3/1,6-glucan, lactic acid bacteria, and ${\beta}$-1,3/1,6-glucan+lactic acid bacteria were tested for 10 weeks using an immunodeficient animal model infected with LP-BM5 murine AIDS virus On the immune activity. Cytokines production, plasma immunoglobulin concentration, T cell and B cell proliferation were measured. As a result, the T cell proliferative capacity which was weakened by immunization with LP-BM5 murine AIDS virus increased significantly T cell proliferative capacity compared with the red ginseng control group. B cell proliferative capacity was significantly higher than the infected control group. Increased B cell proliferation was reduced. In the cytokine production, IL-2, IL-12 and IL-15 in the Th1-type cytokine increased the secretion of IL-2, IL-12 and IL-15 compared to the infected control. The proliferative capacity of the treated group was higher than that of the mixed treatment group. TNF-${\alpha}$ was significantly decreased compared with the infected control group. The IL-4, IL-6 and IL-10 levels were significantly inhibited in the infected control group and the Th1/Th2 type cytokine expression was regulated by immunohistochemistry. IgE, IgA, and IgG levels were significantly lower in the immunoglobulin secretion assay than in the control. As a result, the immunomodulatory effect of ${\beta}$-1,3/1,6-glucan+lactic acid bacteria was confirmed by mixing with LP-BM5 murine AIDS virus-infected immunodeficient animal model.

• Journal of Life Science
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• v.30 no.3
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• pp.267-277
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• 2020

This study was conducted to assess the effect of highly concentrated onion intake on rodents. The experimental animals were divided two groups as follows; water administered group (CON) and Allium cepa administered group (ACE). The ACE group showed a slightly increases in the number of erythrocytes (RBC), hemoglobin (HGB), hematocrit (Hct) levels compared to the control group (p<0.05). Hemoglobin, monocyte, lymphocyte and neutrophil had no significant change (p>0.05) in ACE group and control group. The analysis of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels showed a significant decrease in ACE group compared to the control group (p<0.05). The blood glucose, total protein, HDL-cholesterol were slightly high in ACE group, while triglyceride, total cholesterol levels were lower in ACE group compared to the control group (p<0.05). The levels of cytokines (interluekin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (INF-γ), interleukin-18 (IL-18), interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF)) involved in immunity and inflammation in liver tissue and blood have all been confirmed to be within normal range. These findings could be used as basic data to show that highly concentrated dietary onion extract is not toxic to hematological indicators and immune functions.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.101-109
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• 2013

Objectives : The purpose of this study was to investigate the effects of Polygoni Multiflori Radix Water Extract (PM) on the production of inflammatory mediators in RAW 264.7 mouse macrophages induced by lipopolysaccharide (LPS). Method : We examined effect of PM Extract on the cell viability of RAW 264.7 cells. Futhermore, we investigated anti-inflammatory effect of PM Extract by the production of proinflammatory cytokines such as NO, intracellular calcium, interleukin(IL)-$1{\alpha}$, IL-3, IL-$1{\beta}$, IL-6, interferon inducible protein-10(IP-10), keratinocyte-derived chemokine(KC) and vascular endothelial growth factor(VEGF). Result : No significant changes have been found in the mouse macrophge cell viability by the PM Extract at the concentration of 25, 50, 100 and $200{\mu}g/mL$. The water extract of PM significantly inhibited the production of NO and intracellular calcium in the LPS-induced macrophages at the concentration of 25, 50, 100 and $200{\mu}g/mL$. The water extract of PM significantly inhibited the production of IL-$1{\alpha}$, IL-${\beta}$, IL-3, IP-10, KC, VEGF in the LPS-induced macrophages at the concentration of 50, 100, and $200{\mu}g/mL$; IL-6 at the concentration of 100 and $200{\mu}g/mL$ ; and IL-17 at $200{\mu}g/mL$. Conclusion : The water extract of PM significantly inhibited the production of NO, intracellular calcium, IL-$1{\alpha}$, IL-3, IL-${\beta}$, IP-10, KC, VEGF at the concentration of 50 ㎍/mL or higher in the LPS-induced macrophages with no changes in the cell viability of them. These results suggest that water extract of Polygoni Multiflori Radix has anti-inflammatory effect regulating the production of proinflammatory cytokines in the LPS-induced macrophages.

• BMB Reports
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• v.35 no.6
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• pp.623-628
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• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

• Parasites, Hosts and Diseases
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• v.55 no.6
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• pp.613-622
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• 2017

IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.202-207
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• 2002

Background: Kawasaki disease is an acute febrile illness with systemic vasculitis which primarily affects children, We examined the production of leptin in plasma and gene expressions of CXC chemokines in peripheral blood mononuclear cells from patients with Kawasaki disease. Methods: Consecutive 39 samples from 13 patients according to the different clinical stages (acute, subacute, convalescent) of Kawasaki disease were collected. The plasma leptin levels according to clinical stages of Kawasaki disease were examined by ELISA and the expression of IP-10, Mig and IL-8 mRNAs in 39 samples (13 samples of each stage) from 13 cases were examined by RT-PCR. Results: There were not significant changes of plasma leptin levels according to the clinical stages of Kawasaki disease. The mean values of plasma leptin concentrations during each of the stages (n=13, p>0.05, pg/ml) were $335.8{\pm}549.0$ in acute, $358{\pm}347.6$ in subacute, and $443.6{\pm}645.9$ in convalescent stage. The mRNAs of IP-10, Mig, and IL-8 were expressed in 13/13 (100%), 2/13 (15%), 9/13 (69%) during acute stage, 13/13 (100%), 6/13 (46%), 13/13 (100%) during subacute stage, and 13/13 (100%), 4/13 (31%), 10/13 (77%) during the convalescent stage, respectively. In three patients, the production of leptin and expression of IP-10 mRNA were dramatically decreased according to the process of the clinical stages. In five patients with prominent cervical lymphadenopathy, the expression of IL-8 mRNA during the subacute stage was more elevated than the acute and convalescent stages. Conclusion: This data suggests that the production of leptin and the gene expressions of IP-10, Mig and IL-8 seem to have no significant correlation to the clinical stages of Kawasaki disease. However, expression patterns of IP-10, Mig and IL-8 mRNA may be related to the specific clinical manifestations, and the expression of IP-10 may also be correlated to leptin levels with pericardial involvement.