• Biomolecules & Therapeutics
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• 제23권2호
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• pp.119-127
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• 2015

Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.

• 동의생리병리학회지
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• 제36권2호
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• pp.66-72
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• 2022

Flos Lonicerae Japonicae (the flower buds of Lonicera japonica Thunberg) has been used as an antibacterial and antiviral drug in Korean Medicine. The aim of this study is to evaluate the effect of Flos Lonicerae Japonicae water extract (FL) on the production of cytokines in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). After 24 h treatment, the production of various cytokines from RAW 264.7 was measured with multiplex cytokine assay using Bio-Plex 200 suspension array system. FL at concentrations of 50, 100, and 200 ㎍/mL significantly inhibited productions of tumor necrosis factor-α, macrophage inflammatory protein (MIP)-1β, and MIP-2 in LPS-stimulated RAW 264.7 cells; FL at concentrations of 100 and 200 ㎍/mL significantly inhibited productions of leukemia inhibitory factor, LIX (CXCL5), and RANTES in LPS-stimulated RAW 264.7 cells; FL at concentrations of 200 ㎍/mL significantly inhibited productions of granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor in LPS-stimulated RAW 264.7 cells; FL at concentrations of 50 and 100 ㎍/mL significantly increased productions of interleukin (IL)-10 in LPS-stimulated RAW 264.7 cells; FL at concentrations of 50, 100, and 200 ㎍/mL significantly increased productions of IL-6 and interferon gamma-induced protein-10 in LPS-stimulated RAW 264.7 cells; FL at concentrations of 100 and 200 ㎍/mL significantly increased productions of monocyte chemoattractant protein-1 in LPS-stimulated RAW 264.7 cells. Taken together, these data mean that FL might modulate productions of cytokines, chemokines, and growth factor in LPS-stimulated macrophages. Further study needs to verify the exact mechanism for modulatory activities of FL with macrophages.

• Nutrition Research and Practice
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• 제11권3호
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.

• Nutrition Research and Practice
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• 제17권5호
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• pp.917-933
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• 2023

BACKGROUND/OBJECTIVES: As peanuts germinate, the content of the components beneficial to health, such as resveratrol, increases within the peanut sprout. This study examined whether the ethanol extract of peanut sprout tea (PSTE) inhibits breast cancer growth and metastasis. MATERIALS/METHODS: After orthotopically injecting 4T1 cells into BALB/c mice to induce breast cancer, 0, 30, or 60 mg/kg body weight/day of PSTE was administered orally. Angiogenesis-related protein expression in the tumors and the degree of metastasis were analyzed. 4T1 and RAW 264.7 cells were co-cultured, and reverse transcription polymerase chain reaction was performed to measure the crosstalk between breast cancer cells and macrophages. RESULTS: PSTE reduced tumor growth and lung metastasis. In particular, PSTE decreased matrix metalloproteinase-9, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor-A, F4/80, CD11c, macrophage mannose receptor, macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 expression in the tumors. Moreover, PSTE prevented 4T1 cell migration, invasion, and macrophage activity in RAW 264.7 cells. PSTE inhibited the crosstalk between 4T1 cells and RAW 264.7 cells and promoted the macrophage M1 subtype while inhibiting the M2 subtype. CONCLUSIONS: These results suggest that PSTE blocks breast cancer growth and metastasis to the lungs. This may be because the PSTE treatment inhibits the crosstalk between mammary cancer cells and macrophages and inhibits the differentiation of macrophages into the M2 subtype.

• 대한본초학회지
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• 제22권4호
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• pp.233-238
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• 2007

Objectives : Scutellariae Radix (Hwanggeum in Korean) is the root of Scutellaria baicalensis Georgi. Scutellariae Radix is well known to be used as a medicine for common cold, upper respiratory infections, and to strengthen and regulate the immune system and anemia etc. Little is understood about the roles of Scutellariae Radix in the cytokine and chemokine secretion by immune cells. This study was designed to find out the effects of Scutellariae Radix on the cytokine and chemokine secretion in human mast cells (HMC-1). Methods : We treated hwanggeum according to consistency on HMC-1 and measured cytokines and chemokines levels using flow cytometry CBA system. Results : In hwanggeum treated group, the expression of interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), chemokine (C-X-C motif) ligand 9 (CXCL9, MIG), interleukin 8 (IL-8), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 10 (IL-10), and interferon ${\gamma}$ (IFN-${\gamma}$) were decreased significantly. Conclusion : These results suggest that hwanggeum may support some of immune diseases by means of amiliorating some chemokines or cytokines such as IP-10, MCP-1, MIG, IL-8, IL-2, IL-4, IL-5, IL-10, and IFN-${\gamma}$.

• 대한한방부인과학회지
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• 제27권1호
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• pp.1-16
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• 2014

Objectives: The purpose of this study was to investigate the effects of Gardeniae Fructus Water Extract (GF) on the production of inflammatory mediators in RAW 264.7 cell treated with lipopolysaccharide (LPS). Methods: Gradeniae Fructus was extracted with distilled water (2,000 ml) for 2 hours. In order to evaluate cytotoxicity of GF, 3 - (4,5-dimethylthiazol-2-yl) - 2,5 - diphenyltetrazolium bromide (MTT) assay was performed. To investigate antiinflammatory effects, the concentration of nitric oxide (NO) was measured with No assay, calcium (Ca) was measured with Fluo-4 Ca assay, and cytokine was measured by Bio-Plex cytokine assay in RAW 264.7 cell. And when p-value is below 0.05, it is judged to have the significant difference statistically. Results: 1. GF did not show any cytotoxicity. 2. GF suppressed the production of NO and Ca at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 3. GF suppressed the production of interleukin (IL)-$1{\beta}$, IL-10, IL-12p40, macrophage-colony stimulating factor (M-CSF), macrophage inflammatory protein (MIP)-$1{\beta}$ and keratinocyte chemoattractant(KC) at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 4. GF suppressed the production of vascular endothelial growth factor (VEGF), granulocyte-colony stimulating factor (G-CSF) and monocyte cheomattractant protein (MCP)-1 at the concentration of 25, 50 and $100{\mu}g/ml$. 5. GF suppressed the production of granulocyte macrophage-colony stimulating factor (GM-CSF) and regulated on activation, normal T cell expressed and secreted (RANTES) at the concentration of 25 and $50{\mu}g/ml$. 6. GF suppressed the production of MIP-2 at the concentration of 50 and $100{\mu}g/ml$, and tumor necrosis factor (TNF)-${\alpha}$ at the concentration of 50 and $200{\mu}g/ml$. Conclusions: These results suggest that GF has anti-inflammatory effect and immuno-modulating activity.

• 한국버섯학회지
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• 제14권4호
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• pp.155-161
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• 2016

A recent study reported that Pleurotus ostreatus has the potential to be used as a ${\beta}-glucan-based$ cream for supportive complementary therapy of atopic dermatitis. KH054 is a new herbal prescription consisting of P. ostreatus and Panax ginseng. The effects of atopic dermatitis-induced materials on the expression of cytokine genes in human monocytes (THP-1, EoL- 1) have been examined. Some reports demonstrated that P. ginseng augments the activity of natural killer cells, which plays an important role in innate immunity against infection and tumor development. Monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-6, and IL-8 have important roles in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The present study investigated whether KH054 on induced IL-6, IL-8, and MCP-1 secretion by house dust mite (Dermatophagoides pteronissinus) in THP-1 (human acute monocytic leukemia) and EoL-1(Human eosinophilic leukemia) cell. D. pteronissinus functions in the pathogenesis of allergic diseases, including atopic dermatitis and asthma. The inhibitory effect of KH054 on the induction of IL-6, IL-8, and MCP-1 secretion by D. pteronissinus extract in THP-1 and EoL-1 cells was examined. KH054 potently suppressed the elevated production of IL-6 and IL-8 induced by D. pteronissinus treatment in THP-1 and EoL-1 cells. Based on the present results, KH054 may be useful for developing functional foods to treat atopic dermatitis.

• Restorative Dentistry and Endodontics
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• 제30권3호
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• pp.193-203
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• 2005

본 연구에서는 발거된 건전한 치아의 치수조직으로부터 배양된 치수조직을 SP 및 TNF (tumor necrosis factor)-${\alpha}$, 그리고 Spantide로 15분간 배양 후 SP로 36시간 자극하여 IL-8은 및 MCP-1의 분비량을 측정하였으며, 면역염색으로 IL-8의 분비를 관찰하여 다음과 같은 결론을 얻었다. 1. 치수 조직을 SP (10$^{-4}$M)로 36시간 자극 시 모의 자극에 비해 IL-8이 현저히 증가하였으며 (p < 0.05), 면역 염색 결과 모의 자극 시에는 치수조직의 변연부에만, SP(10$^{-4}$M)로 36시간 자극시에는 flbroblast 주위로 IL-8의 발현이 관찰되었다. 2. TNF-${\alpha}$ (40 ng/ml)로 치수조직을 36시간 자극시 모의 자극에 비해 MCP-1이 증가하였으며, SP에서는 증가 를 보이지 않았으며 (p < 0.05), 면역 염색 결과 IL-8의 발현이 관찰되지 않았으며, 치수 조직의 변연부를 따라서 약한 IL-8의 발현이 관찰되었다. 3. Spantide (10$^{-5}$ M)는 SP (10$^{-4}$ M)로 치수 조직을 36시간 자극 시 IL-8의 분비를 억제하였다.

• 한국환경보건학회지
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• 제48권2호
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• pp.106-115
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• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.

• Nutrition Research and Practice
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• 제18권1호
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• pp.1-18
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• 2024

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)₂D₃ after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)₂D₃ during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)₂D₃ treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)₂D₃ administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)₂D₃ inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)₂D₃ treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)₂D₃ prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.