• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.163-170
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• 2016

We examined whether apigenin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the knee joint of rat to evaluate the potential chondroprotective effects of apigenin. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription - polymerase chain reaction (RT-PCR) was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and ADAMTS-5. In rabbit articular chondrocytes, the effects of apigenin on IL-$1{\beta}$-induced secretion and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of apigenin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, apigenin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Furthermore, apigenin inhibited the secretion and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that apigenin can regulate the gene expression, secretion, and activity of MMP-3, by directly acting on articular chondrocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6409-6413
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• 2012

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5075-5079
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• 2012

Purpose: The results of recent published studies focusing on IL-8 polymorphism in colorectal cancer susceptibility have often been inconsistent. We therefore carried out a meta-analysis based on independent studies to assess the association. Methods: Nine case-control studies with 7,003 individuals (3,019 cases and 3,984 controls) were included in this meta-analysis through searching the databases of PubMed, Excerpta Medica Database (EMBASE), and Chinese Biomedical Literature Database (CBM; Chinese) (up to Aug 1st, 2012). The odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of the association. Meta-analysis was conducted in a fixed/random effect model. Results: No obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (for A vs. T: OR = 1.084, 95% CI = 0.971-1.209, P = 0.019; for TA vs. TT: OR = 1.18, 95% CI = 0.943-1.475, P = 0.001; for AA vs. TT: OR = 1.155, 95% CI = 0.916-1.456, P = 0.014; for AA+TA vs. TT: OR = 1.170, 95% CI =0.953-1.437, P = 0.001; for AA vs. TT+TA: OR = 1.044, 95% CI = 0.886-1.230, P = 0.097). In the subgroup analyses by ethnicity (Caucasian) and source of controls (population based), also no significant associations were found for all genetic models. Conclusions: Result suggests that the IL-8-251T>A polymorphism is not associated with colorectal cancer risk. Because of the limitations of this meta-analysis, this finding demands further investigation.

• The Korea Journal of Herbology
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• v.28 no.5
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• pp.39-44
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• 2013

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease. The purpose of this study was to investigate the anti-allergic effect of fermented Angelicae gigantis Radix in human mast cell line, HMC-1. Method : The Angelicae gigantis Radix was fermented by Lactobacillus acidophilus. The cell toxicity of fermented Angelicae gigantis Radix(FAGR) was determined by MTT assay. The release of ${\beta}$-hexosaminidase from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by ${\beta}$-hexosaminidase assay. Also, the concentrations of cytokines (interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha) were measured by enzyme-linked immunosorbent assay. The gene expression of COX-2 from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by reverse transcription polymerase chain reaction. The release of histamine on substance P-stimulated HMC-1 was measured by histamine assay. Result : The FAGR suppressed the release of ${\beta}$-hexosaminidase, a marker of degranulation, from HMC-1 stimulated by PMA plus A23187. The FAGR inhibited the production of interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha. The FAGR inhibited the expression of COX-2 mRNA. The FAGR suppressed the release of histamine on substance P-stimulated HMC-1. Conclusion : These results provide that FAGR may be beneficial in the treatment of allergic inflammatory disease.

• 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.

• Korean Journal of Agricultural Science
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• v.45 no.3
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• pp.437-446
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• 2018

Lactoferrin is an iron-binding glycoprotein which is present in colostrum, milk, and other body secretions. Lactoferrin activities are associated with inflammatory and immune responses. The aim of this study was to investigate the effect of lactoferrin hydrolysates (LH) on the production of immunomodulatory factors such as inflammatory related cytokines (tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, interleukin (IL)-6, and interleukin (IL)-13) in Raw264.7 cells, which originated from murine macrophages. The results show that the Raw264.7 cells cultured in 3 types (whole, and above and below 10 kDa) of lactoferrin hydrolysates (LH) did not show any cytotoxicity in the cells. $TNF-{\alpha}$ decreased dose-dependently to 1,500 - 2,000 ng/mL by treatment with the 3 types of LH at 1, 50, $100{\mu}g/mL$, whereas the positive control, lipopolysaccharide (LPS), and negative control produced 2,450 and 1,000 ng/mL of $TNF-{\alpha}$, respectively, in the Raw264.7 cells. The treatment with the 3 types of LH (whole and above and below 10 kDa) at $50{\mu}g/mL$ produced about 20 - 28 ng/mL of $IL-1{\beta}$ at 3, 6, and 9 h, respectively, while the negative control produced 7 ng/mL, and LPS as the positive control produced 48 - 60 ng/mL. $TNF-{\alpha}$ and IL-6 expression was decreased dose-dependently by the 3 types of LH. The mRNA levels of IL-13 were slightly increased dose-dependently by the whole and above 10 kDa LH, but decreased dose-dependently by the below 10 kDa LH in the Raw264.7 cells. The results show that LH had immunomodulating effects on cytokine production in anti- and pro-inflammatory reactions as well as anti-allergic reactions.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.23 no.4
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• pp.393-401
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• 2013

Objectives: Endotoxins in dust generated in occupational settings is known to contribute to the occurrence of respiratory illness among workers. The relationship between the level of endotoxins in total dust or respirable particulates collected from swine farms and immunological markers related with respiratory allergy was evaluated among swine husbandry workers. Materials and Methods: Peripheral blood samples were collected from ten workers at ten swine farms at Gyeonggi province, Korea. Peripheral mononuclear cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 48 hours. The levels of various cytokines produced at culture supernatants were determined using a commercially available ELISA kit. The concentration of particulate matter($PM_{10}$) in the indoor air of the swine farms was evaluated using a PVC membrane filter and mini volume air sampler, and endotoxin levels in the dust were measured by Limulus Amebocyte Lysate Kinetic QCL method. Results: Levels of endotoxins in the total dust were categorized into high(geometric mean: $109.35EU/m^3$) and low concentrations (geometric mean: $0.95EU/m^3$) for five swine farms. Interleukin-4 levels were higher in the high endotoxin group than in the low endotoxin group, while interferon-${\gamma}$ levels were lower in the high endotoxin group than in the low endotoxin group. The ratio (interferon-${\gamma}$ to interleukin-4), indicating immunologic skewedness against allergic reactivities, was lower in the high endotoxin group($1.15{\pm}0.60$) than the low endotoxin group($3.09{\pm}2.38$). In addition, the level of interleukin-13, another cytokine contributing to the occurrence of allergic responses, was significantly higher in the at the high endotoxin group($1.12{\pm}0.37ng/m{\ell}$) than in the low endotoxin group($0.37{\pm}0.04ng/m{\ell}$). Hematologic assessment showed significantly lower cellularity in the number of total leukocytes, neutrophils, and eosinophils in the high endotoxin group than in the low endotoxin group. Conclusions: Even though a sufficient number of swine workers and farms were not investigated, this study generlly suggests that the immunological function of swine farm workers exposed to high levels of endotoxin could be modulated toward allergic reactivities.

• Clinical and Experimental Pediatrics
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• v.53 no.1
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• pp.41-47
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• 2010

Purpose : Adiponectin is an endogenous modulator of vascular remodeling that suppresses vascular inflammation. However, the role of adiponectin in Kawasaki disease (KD) has not been elucidated. The purpose of this study is to investigate the correlation between serum adiponectin level and several parameters, such as interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, lipid profile, and C reactive protein (CRP), and to clarify the association between adiponectin and cardiac function. Methods : Twenty-two KD patients (22 patients in acute phase and 20 patients in subacute phase) were enrolled in the study group. The control group consisted of 31 subjects (13 febrile patients and 18 healthy children). Both groups underwent blood sampling and tissue Doppler imaging (TDI). Results : CRP was significantly increased in the KD group compared with the control group. There were no significant differences in serum $TNF-{\alpha}$, IL-6, and adiponectin levels between groups. However, a negative correlation was found between adiponectin level and CRP level or platelet count. Systolic myocardial velocity and A myocardial velocity measured by TDI were decreased significantly in the acute KD group compared with the subacute KD group and control group. Positive correlations were found between adiponectin level and systolic myocardial velocity or A myocardial velocity. Conclusion : In acute KD patients, low adiponectin level was related to severe inflammatory reactions and decreased left ventricular functions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3495-3499
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• 2012

The aim of this study was to evaluate the diagnostic value of interleukin 21(IL-21) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 103 patients were classified on the basis of diagnosis as TPE (n=51) and MPE (n=52). The concentration of IL-21 was determined by ELISA. Lactate dehydrogenase (LDH), adenosine dehydrogenase (ADA) and CEA levels were also determined in all patients. A significant difference was observed in the levels of ADA and CEA (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The concentration of IL-21 in MPE was significantly higher compared to TPE (P<0.01). With a threshold value of 4.32 pg/ml, IL-21 had a sensitivity of 76.9% (40/52) and a specificity of 80.4% (41/51). Combined detection of IL-21 and CEA had a sensitivity of 69.2% (36/52) and a specificity of 92.2% (47/51). These two markers can contribute to the differential diagnosis of MPEs.

• Journal of Evidence-Based Herbal Medicine
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• v.1 no.1
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• pp.13-18
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• 2008

Polygoni cuspidati Rhizoma (PCRH) has been used in treatment of menoxenia, skin burn, gallstone, hepatitis, hyperlipidaemia, favus athlete's foot, supperative dermatitis and inflammation. However, its effect in experimental models remains unknown. In this present study, the effect of PCRH for stability on mast cell was analyzed. Two g/kg PCRH inhibited the compound 48/80-induced anaphylaxis by 75%. In addition, PCRH inhibited the tumor necrosis factor-$\alpha$ and interleukin-8 secretion as compared with the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 stimulated human mast cell line, HMC-1 cells. These results suggested PCRH may inhibit mast cell-mediated anaphylactic reaction.