• Molecules and Cells
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• v.38 no.5
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• pp.452-456
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• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.721-727
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• 2007

Scorpion (SCP) has been clinically used for the treatment of endogenous wind to relieve convulsion, clearing away toxins, resolving hard masses and removing obstruction in the collaterals to relieve pain. Recent studies showed that scorpion toxins that affect the activating mechanism of sodium channels and indian black scorpion venom induced anti-proliferative and apoptogenic activity against human leukemic cell lines U937 and K562. There is lack of studies regarding the effects of SCP on the immunological activities. The present study was conducted to evaluate the effect of SCP on the regulatory effects of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of SCP MeOH extract dissolved in media for 1 h prior to the addition of lipopolysaccharide (LPS: 1 ${\mu}$g/ml), cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) was determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. As results, SCP inhibited the production of nitrite and nitrate (0.3 and 1.0 mg/ml), iNOS and p-$I_KB_{\alpha}$ protein, tumor necrosis factor-${\alpha}$ (0.3 and 1.0 mg/ml), interleukin-1${\beta}$ (0.3 and 1.0 mg/ml) and interleukin-6 (1.0mg/ml) in Raw 264.7 cells activated with LPS. These findings suggest that SCP can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• IMMUNE NETWORK
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• v.10 no.2
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• pp.76-81
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• 2010

Ultraviolet B (UVB) induces multiple inflammatory and carcinogenic reactions. In skin, UVB induces to secrete several kinds of inflammatory cytokines from keratinocytes and also increases angiogenic process via the modulation of vascular endothelial growth factor (VEGF) production. Interleukin-21 (IL-21) is an inflammatory cytokine and produced by activated T cells. The biologic functions of IL-21 have not yet extensively studied. In the present study, we investigate the production of IL-21 from human keratinocyte cell line, HaCaT and its biological effect after exposure to UVB. First, we confirmed the IL-21 production and its receptor expression in HaCaT. And then, the change of IL-21 and VEGF production in HaCaT by UVB irradiation was examined. Not only IL-21 but also VEGF production was enhanced by UVB irradiation. Next, to determine relationship of enhanced production of IL-21 and VEGF, we detected VEGF production after neutralization of IL-21. VEGF production was reduced by IL-21 neutralization, which indicates that the IL-21 is involved in the VEGF production. Taken together, our results suggest that IL-21 and VEGF production is enhanced by UVB irradiation in HaCaT. In addition, it seems that IL-21 plays a role in the angiogenic process in skin via the modulation of VEGF production.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.196-202
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• 1999

The purpose of the study was to determine the effect of vitamin B complex on stress-induced immune alteration. 21 medical students participated in the study 4 weeks before an academic examination period(baseline), 2 weeks before the exam period and during the exam period. Among them, 10 subjects were given vitamin B complex for 4 weeks, and 11 were not given vitamin B during the whole period. Cell-mediated immune function was measured by lymphocyte proliferative response to phytohemagglutinin(PHA) and interleukin-2(IL-2) production. Global assessment of recent stress(GARS) scale and symptom checklist-90-revised(SCL-90-R) were used to measure the level of subjective stress and psychopathology. Vitamin group had significantly lower scores of anxiety scale on SCL-90-R than non-vitamin group. No significant differences were found in lymphocyte proliferative response to PHA and IL-2 production between vitamin and non-vitamin groups during each period. There were no significant differences in change of of each of the two immune parameters over time as well as between vitamin and non-vitamin groups. However, lymphocyte proliferative response to PHA was significantly increased over time. In conclusion, it was suggested that vitamin B complex is likely to decrease anxiety level, and that exam stress might enhance lymphocyte proliferation regardless of vitamin B.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.54-59
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• 2007

In this paper, we present evidence that the Korean red ginseng extract shows the immunomodulatory activities during postoperative chemotherapy after curative surgery in patients with advanced colon cancer. We measured the circulating interleukin-2 (IL-2), interleukin-8 (IL-8)and interleukin-10 (IL-10) as a immune modulator to evaluate the effect of Korean red ginseng. The mean preoperative value of IL-2 was similar in the non-RG group and the RG group (5.72 pg/ml versus 6.87 pg/ml, p>0.05). The mean value of IL-2 was compared with IL-2 from healthy control group, there was no significant difference (14.89 pg/ml versus 14.22 pg/ml, p>0.05). The mean preoperative value of IL-8 was higher in the non-RG group comparing with the RG group (30.92 pg/ml versus 36.25 pg/ml, p < 0.05). At postoperative 3 month, the mean values of IL-8 from non-RG and RG group down to 24.56 pg/ml and 21.46 pg/ml respectively. The IL-8 of RG group at 3 month showed no difference with that of HC group(21.46 pg/ml versus 16.31 pg/ml, p>0.05). The preoperative mean value of IL-10 of non-RG, RG and HC group was 11.56 pg/ml, 10.8 pg/ml, and 3.68 pg/ml respectively. At postoperative 3 month, the mean values of IL-10 from non-RG and RG group down to 8.45 pg/ml and 5.04 pg/ml respectively. In spite of decreasing IL-10 levels of both cancer Patients group with time, there was still significant difference with that of HC group (non-RG versus HC group, p=0.00, RC versus HC group, p=0.04). The results of this study suggest that the red ginseng extract may have some immunomodulatory properties associated with IL-2, IL-8 and IL-10 activity in patients with advanced colorectal cancer during postoperative chemotherapy. We think to need the further studies and a larger sample size to fully evaluate the antitumor effect of ginseng and need to establish this mechanism of action as well as identify the active components associated with antitumor activity and immunomodulation in patients with advanced colorectal cancer.

• Journal of Life Science
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• v.21 no.7
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• pp.1039-1045
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• 2011

The effects of duration and time-dependent, high-intensity exercise on hematological properties and inflammation-related parameters in rats were studied. 20, 60, and 120 min of high-intensive exercise were performed daily for 8 weeks. None of the complete blood count (CBC) factors were affected by the exercise, except for the leukocyte concentration which, in the 20 min group, showed an increase of 47% compared to the control, but this was decreased after 60 min by 30% compared to the control. As exercise was performed for 60 min or longer, serum concentrations of $Fe^{++}$, unsaturated iron biding capacity (UIBC), and total iron biding capacity (TIBC) were significantly elevated in comparison to the control, where 20 min of exercise did not show any change. Both levels of interleukin-6 (IL-6), a pro-inflammatory cytokine, and interleukin-10 (IL-10), an anti-inflammatory cytokine in the serum, were elevated in response to the high-intensity exercise, however the rate of IL-6 increase was higher than the rate of exercise intensity increase, thus the offset of inflammation might be suggested. The concentration of nitric oxide (NO) in the serum became high in response to the exercise. Overall, the current observation suggests that inflammation-like responses to high-intensity exercise might be due to high circulation of blood flow and high oxygen requirement, resulting in systemic damages. However, under the current high-intensity exercise conditions, more than 20 min of exercise might not be suggested for health care purposes.

• Biomedical Science Letters
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• v.21 no.4
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• pp.218-226
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• 2015

The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.12
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• pp.1718-1728
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• 2011

Two experiments were conducted to investigate the in vitro ability of keratinase to hydrolyze soybean glycinin and ${\beta}$-conglycinin and to evaluate the in vivo effects of keratinase when included in corn-soybean diets with different levels of crude protein and fed to nursery pigs. In experiment 1, a saturated keratinase solution (1 ml) was added to two blank controls of either glycinin or ${\beta}$-conglycinin resulting in the hydrolysis of 94.74% glycinin and 88.89% ${\beta}$-conglycinin. In experiment 2, 190 pigs (8.3${\pm}$0.63 kg BW) were allotted to one of four treatments in a 2${\times}$2 factorial arrangement on the basis of body weight, and sex was balanced among the pens. The effects of crude protein (19 vs. 22%) and keratinase (0 vs. 0.05%) were studied. Each treatment was applied to six pens with seven (two pens) or eight pigs per pen. Pigs were fed the experimental diets for 21 d. Weight gain and feed conversion ratio were improved (p<0.05) with keratinase supplementation while feed intake was reduced (p<0.05). Keratinase supplementation increased (p<0.05) the apparent total tract digestibility of dry matter, energy, crude protein and phosphorus. Keratinase supplementation also increased n-butyric acid in the cecum and colon, lactobacilli and total anaerobe counts in the colon as well as the ratio of villus height to crypt depth in the ileum. Additionally, fecal score, ammonia nitrogen and branch chain volatile fatty acids in the colon, E. coli and total aerobe counts in the colon, crypt depth in the jejunum and ileum as well as serum interleukin-1 and interleukin-6 concentrations were also decreased (p<0.05) by keratinase supplementation. A reduction in dietary crude protein decreased (p<0.05) colon ammonia nitrogen concentration and cecal propionic acid and branch chain volatile fatty acid concentrations. In addition, cecal E. coli counts, colon total anaerobe counts, ileal crypt depth, and serum interleukin-1 and interleukin-6 concentrations were also decreased (p<0.05) with the reduction of dietary crude protein. With the exception of fecal scores, there were no significant interactions between crude protein and keratinase. This study provides evidence that dietary keratinase supplementation improved nursery pig performance by improving intestinal morphology and ecology, thus improving nutrient digestibility and alleviating the inflammatory response.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.4
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• pp.332-344
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• 1999

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Interleukin-8 (IL-8) is a neutrophil chemotactic factor that plays an important role in the recruitment of neutrophil to inflammatory loci. Inflammatory mediators by cells in the gingiva have been implicated in the initiation and progression of periodontitis and oral infection. The purpose of this study was conducted to investigate the effect of lipopolysaccharide (LPS), staphylococcus enterotoxin B (SEB) on production of IL-6 and IL-8 by human gingival and facial dermal fibroblasts. Primary cultured human gingival and facial dermal fibroblasts were incubated with LPS (0.01, 0.1, $1.0{\mu}g/ml$), SEB (0.01, 0.1, $1.0{\mu}g/ml$) or LPS $(0.1{\mu}g/ml)$ plus SEB $(0.1{\mu}g/ml)$. Culture supernatants were collected at 24, 48, and 72 hrs and assessed for IL-6 and IL-8 production by enzyme-linked immunosorbent assay. IL-6 production in gingival fibroblasts stimulated with LPS was higher than that with SEB. IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-6 production in facial dermal fibroblasts was increased only by stimulation with a high concentration of LPS $(1.0{\mu}g/ml)$. Its production in facial dermal fibroblasts by exposure with SEB was decreased in comparison with control, nontreated cells. Therefore, gingival fibroblasts showed higher sensitivity than facial dermal fibroblasts in response to low concentration of LPS. Also, IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in gingival fibroblasts was enhanced greatly only by stimulation of high concentration of LPS $(1.0{\mu}g/ml)$. That by exposure with SEB was increased only in 24 hrs cultivation. IL-8 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in facial dermal fibroblasts was decreased by LPS and increased only in 48 hrs cultivation by SEB. IL-8 production by double exposure with LPS plus SEB was enhanced only in 48 hrs cultivation in comparison with single exposure of LPS or SEB. therefore, IL-6 and IL-8 production were released at various quantities according to bacterial toxin applied and site of fibroblast harvested. These results suggest that gingival fibroblasts may be concerned with IL-6 and IL-8 related inflammatory response more than facial dermal fibroblasts.

• Journal of Periodontal and Implant Science
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• v.44 no.3
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• pp.126-133
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• 2014

Purpose: Smokeless tobacco-based oral-use products like gutka are popular in India. Gutka usage leads to increased periodontal destruction and inflammation; however, the relevant mechanism remains unknown. This study aimed to elucidate the role of gutka in periodontitis by examining its effect on the levels of interleukin (IL) $1{\beta}$ and IL-8 from the gingival crevicular fluid (GCF). Methods: A total of 45 patients were enrolled in this study. Thirty patients with periodontitis (15 gutka chewers [GCP] and 15 nongutka chewers [NGC]) and 15 periodontally healthy controls (HC) were selected. The full-mouth plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and recession (RC) were recorded. The IL-$1{\beta}$ and IL-8 levels in the GCF of all subjects were assessed through an enzyme-linked immunosorbent assay (Quantikine). Results: The IL-$1{\beta}$ and IL-8 levels were not significantly higher in the GCP group (IL-$1{\beta}$, $369.01{\pm}273.44{\mu}L$; IL-8, $205.97{\pm}196.78{\mu}L$) as compared to those in the NGC group (IL-$1{\beta}$, $195.57{\pm}96.85{\mu}L$; IL-8, $178.61{\pm}149.35{\mu}L$). More gingival RC and loss of attachment was seen among the GCP group (RC: $2.02{\pm}0.31$, P=0.013; CAL: $4.60{\pm}0.56$, P<0.001) than among the NGC group (RC, $1.21{\pm}1.15$; CAL, $3.70{\pm}0.32$); however, PD was deeper among the NGC subjects (P=0.002). PI and GI were significantly higher for the periodontitis group (P<0.001) when compared to the HC, but there was no difference among gutka chewers and non-chewers (P=0.22 and P=0.89). A positive correlation was found between the IL-8 levels and the duration of gutka chewing (r=-0.64, P<0.01). Conclusions: Gutka chewing leads to increased gingival RC and clinical loss of attachment. There was no effect seen in the proinflammatory cytokine levels in the GCF of gutka users.