• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.253-259
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• 2019

Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.275-283
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• 2012

Background: Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease. Methods: Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways. Results: Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-${\alpha}$, IL-6, and IL-10 were significantly lower. Conclusion: Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.

• Natural Product Sciences
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• v.23 no.1
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• pp.1-4
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• 2017

Sinensetin, a pentamethoxyflavone, is known to exert various pharmacological activities including anti-angiogenesis, anti-diabetic and anti-inflammatory activities. However, its effects on the human mast cell - 1 (HMC-1) mediated inflammatory mechanism remain unknown. To explore the mediator and cellular inflammatory response of sinensetin, we examined its influence on phorbol 12-myristate 13-acetate (PMA) plus A23187 induced inflammatory mediator production in a human mast cell line. In this study, interleukin (IL)-6 production was measured using the enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Sinensetin inhibited PMA plus A23187 induced IL-6 production in a dose-dependent manner as well as IL-4, IL-5 and IL-8 mRNA expression. Furthermore, sinensetin inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, suggesting that sinensetin inhibits the production of inflammatory mediators by blocking STAT3 phosphorylation. Moreover, sinensetin was found to inhibit nuclear factor kappa B activation. These findings suggest that sinensetin may be involved in the regulation of mast cell-mediated inflammatory responses.

• Restorative Dentistry and Endodontics
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• v.32 no.3
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• pp.191-197
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• 2007

Mineral trioxide aggregate (MTA) would influence healing of periapical tissues by modulating the production of growth factors and cytokines from PDL fibroblasts, however, the studies are insufficient. Therefore, the purpose of this study was to monitor the expression of transforming growth factor-beta1 $(TGF-\beta1)$, fibroblast growth factor-2 (FGF-2), and interleukin-6 (IL-6) from PDL fibroblasts in the presence of MTA. The human PDL fibroblasts were seeded onto the set MTA or IRM at a level of $1\times10^5$ cells per unit well, and further incubated for 6, 12, 24, and 48 hours. The levels of $TGF-\beta1$, FGF-2 and IL-6 from the supernatant were measured by enzyme-linked immunosorbent assay (ELISA) The data were analyzed using one-way ANOVA. The level of $TGF-\beta1$ was down-reg ulated when the cells were grown in the presence of MTA except at 6 hours. The levels of FGF-2 release were significantly suppressed when PDL fibroblasts were grown in the presence of MTA or IRM at all time intervals (p < 0.05). The expressions of IL-6 from MTA treated co)Is were comparable to those of untreated control cells throughout the observation periods. We presume that this material inhibits the stimulatory function of growth factors on granulation tissue formation and in turn, it promotes the healing process modulated by other bone-remodeling cells.

• Advances in Traditional Medicine
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• v.5 no.4
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• pp.251-261
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• 2005

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. RA is characterized by chronic inflammation of the synovial membrane in the joint, which leads to the progressive destruction of articular cartilage, ligament and bone. Several cytokines such as tumor necrosis $factor-{\alpha}\;TNF-{\alpha}\;and\;interleukin-1{\beta}\;(IL-1{\beta})$ and interleukin-6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. Genome wide screening of subjects suffering from autoimmune diseases especially arthritis revealed linkage to inflammatory molecules like $TNF-{\alpha},\;IL-1{\beta}$ and IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB $(NF-{\kappa}B)$ and human leucocyte antigen/major histocompatibility complex (HLA/MHC) locus. The status of the pharmacological mechanism of herbal drugs in the light of genome wide screening results has been discussed to reinforce the therapeutic potential and the pharmacological basis of the herbal drugs.

• KSBB Journal
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• v.30 no.6
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• pp.332-338
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• 2015

The objective of this study was designed to determine the possibility of bioethanol production from wasted medium density fiberboard (wMDF). We were investigated the enzymatic saccharification characteristics using the enzyme (Cellic CTec3) after pretreatment with sodium chlorite. According to the component analysis results, the lignin contents before and after the pretreatment of wMDF (milling using sieve size of $1,000{\mu}m$) was significantly reduced from 31.13% to 4.11%. Therefore, delignification ratio of pretreated wMDF was found to be up to about 87-89% depending on the sieve size. And we were tested to compare the saccharification ratio according to the sieve size of wMDF ($1,000{\mu}m$, $200{\mu}m$), but it was no significance depending on the sieve size. When enzyme dosage was 5% based on the substrate concentration, enzymatic saccharification ratio was obtained up to 70% by maintaining at $50^{\circ}C$ for 72 hours. We could made the substrate concentration of pretreated wMDF ($1,000{\mu}m$) up to 12% and then enzymatic saccharification ratio was 76.8%, also contents of glucose and xylose were analyzed to 77,750 and 14,637 mg/L, respectively.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.44-52
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• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Biomedical Science Letters
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• v.25 no.1
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• pp.15-22
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• 2019

The diagnosis of atopic dermatitis (AD) includes a test that checks allergen-mediated skin reactions and a method of measuring the total IgE and allergen-specific IgE in blood. However, these test methods are performed directly on the patient, which cause some pain or discomfort. In addition, the skin response test or IgE may result in false negative in about 20% of patients. In the present study, to identify specific biomarkers, HaCaT cells were used as a human keratinocyte that make up the skin, were treated IL-4 and IL-13 for 24 hours to induce a situation similar to keratinocytes in AD patients. In the HaCaT cells, pro-inflammatory cytokine such as IL-5, IL-6, and MCP-1 were increased by IL-4 and IL-13 and skin barrier proteins was reduced by IL-4 and L-13. This results showed that a situation similar to the stratum corneum of an actual patient is induced in HaCaT cells. And then the secretions of Kallikrein (KLK) 5 and KLK7 protease were checked by enzyme-linked immunosorbent assay (ELISA). It was specifically increased by IL-4 and IL-13. This showed that AD-related protease can be detected at the protein level using keratinocytes that can be taken in a non-invasive manner and suggested the possibility of applying it to AD diagnosis.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1084-1098
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• 2023

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.3
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• pp.15-28
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• 2021

Objectives: This study was designed to examine the anti-cancer activity by innate immunomodulating and anti-inflammatory effects of liriopis tuber water extract (LPE). Methods: Cell cytotoxicity was tested with 4T1 mouse mammary carcinoma cells, spleen cells, macrophage, and RAW264.7 cells. To investigate innate immunomodulating effects of LPE on macrophage, we measured tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-10 (IL-10). To investigate innate immunomodulating effects of LPE on RAW264.7 cell, we measured TNF-α, interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with LPE to observe innate immunomodulating effect of LPE on RAW264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In an in vitro cytotoxicity analysis, LPE affected tumor cell growth above specific concentration. As compared with the control group, the production of TNF-α, IL-12, and IL-10 were increased in macrophage. As compared with the control group, the production of TNF-α and IL-6 were increased in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating LPE was decreased. In addition, treatment of RAW 264.7 cell with LPE increased the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38. Conclusions: LPE might have impact on the anti-cancer effect by activation of innate immune system and inflammation control.