• 제목/요약/키워드: tumor necrosis factor-{\alpha}

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으뜸도라지추출물이 RBL-2H3 세포에서 탈과립과 염증매개물질의 분비 억제에 미치는 영향 (Inhibitory effect of the aqueous extract of a tetraploid 'etteum' variety in Platycodon grandiflorum on degranulation and inflammatory mediator release in RBL-2H3 cells)

  • 정재인;김형서;지한결;이현숙;이재용;김은지
    • Journal of Nutrition and Health
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    • 제51권3호
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    • pp.208-214
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    • 2018
  • 본 연구는 으뜸도라지추출물의 항알레르기 효과를 조사하기 위해 실시하였다. 으뜸도라지추출물 (50, 100 및 $200{\mu}g/mL$) 처리에 따른 RBL-2H3 비만세포의 세포독성을 조사한 결과 으뜸도라지추출물은 모든 농도에서 세포독성이 관찰되지 않았고, ${\beta}$-hexosaminidase assay를 통해 비만세포의 탈과립 억제능을 평가한 결과 재래종도라지추출물과 비교하여 ${\beta}$-hexosaminidase 억제능이 10배 뛰어남을 확인 하였다. 또한 으뜸도라지추출물은 RBL-2H3 비만세포에서 탈과립 후 유리되는 대표물질인 IL-4, $TNF-{\alpha}$, $PGE_2$$LTB_4$의 생성 분비를 현저히 감소시켰고, 이러한 효과는 재래종도라지와 비교하여 월등한 것으로 나타났다. 이상의 결과는 으뜸도라지추출물이 알레르기 반응을 효과적으로 억제함을 제시하며 향후 항알레르기 기능성 소재로 개발 가능성이 있음을 나타낸다.

Agrobacterium sp.-derived β-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study

  • Lee, Yeon Joo;Paik, Doo-Jin;Kwon, Dae Young;Yang, Hye Jeong;Park, Yongsoon
    • Nutrition Research and Practice
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    • 제11권1호
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    • pp.43-50
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    • 2017
  • BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ${\beta}$-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of $4,000-8,000cells/{\mu}L$ were participated and randomly assigned to take two capsules per day containing either 350 mg ${\beta}$-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-${\gamma}$, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-${\alpha}$ were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ${\beta}$-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ${\beta}$-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ${\beta}$-1,3-glucan did not significantly modulate the levels of IFN-${\gamma}$, IL-2, IL-4, IL-6, IL-12, TNF-${\alpha}$ and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ${\beta}$-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.

Time-dependent proteomic and genomic alterations in Toll-like receptor-4-activated human chondrocytes: increased expression of lamin A/C and annexins

  • Ha, Seung Hee;Kim, Hyoung Kyu;Nguyen, Thi Tuyet Anh;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권5호
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    • pp.531-546
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    • 2017
  • Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases the catabolic compartment and leads to matrix degradation during the development of osteoarthritis. In this study, we determined the proteomic and genomic alterations in human chondrocytes during lipopolysaccharide (LPS)-induced inflammation to elucidate the underlying mechanisms and consequences of TLR-4 activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by real-time PCR analysis of increased interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor alpha ($TNF-{\alpha}$) expression levels. In TLR-4-activated chondrocytes, proteomic changes were determined by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectroscopy analysis, and genomic changes were determined by microarray and gene ontology analyses. Proteomics analysis identified 26 proteins with significantly altered expression levels; these proteins were related to the cytoskeleton and oxidative stress responses. Gene ontology analysis indicated that LPS treatment altered specific functional pathways including 'chemotaxis', 'hematopoietic organ development', 'positive regulation of cell proliferation', and 'regulation of cytokine biosynthetic process'. Nine of the 26 identified proteins displayed the same increased expression patterns in both proteomics and genomics analyses. Western blot analysis confirmed the LPS-induced increases in expression levels of lamin A/C and annexins 4/5/6. In conclusion, this study identified the time-dependent genomic, proteomic, and functional pathway alterations that occur in chondrocytes during LPS-induced TLR-4 activation. These results provide valuable new insights into the underlying mechanisms that control the development and progression of osteoarthritis.

Suppressive effects of $Schizandra$ $chinensis$ Baillon water extract on allergy-related cytokine generation and degranulation in IgE-antigen complex-stimulated RBL-2H3 cells

  • Chung, Mi-Ja;Kim, Jeong-Mi;Lee, Sang-Chul;Kim, Tae-Woo;Kim, Dae-Jung;Baek, Jong-Mi;Kim, Tae-Hyuk;Lee, Jae-Sung;Kim, Kyoung-Kon;Yoon, Jin-A;Choe, Myeon
    • Nutrition Research and Practice
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    • 제6권2호
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    • pp.97-105
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    • 2012
  • $Schizandra$ $chinensis$ Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a $Schizandra$ $chinensis$ Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited ${\beta}$-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-${\alpha}$) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries.

2,3,7,8-tetrachlorodibenzo-p-dioxin 노출과 관련한 인체면역기능 변화를 판단할 수 있는 지표치 개발에 관한 연구 (Immune-alteration Demonstrated at the Korean Vietnam War Veterans Exposed to Agent Orange)

  • 허용;김은미;유지연;홍승권;전성훈;김형아;조대현;한순영
    • 한국환경성돌연변이발암원학회지
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    • 제22권2호
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    • pp.112-124
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    • 2002
  • 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to exert detrimental toxicities on various organ systems including reproductive, cardiovascular, nervous, or dermal system. Immunomodulatory effects of TCDD is thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation and activation, which were demonstrated using experimental animals, whereas immunotoxicity in human has not been investigated well. This study was proceeded to evaluate general immunologic spectrum of the Korean Vietnam War veterans exposed to TCDD during their operation, and compare with that of the non-exposed control subjects with similar age. Regarding composition and quantity, immune cells in peripheral blood collected from the TCDD-exposed was not much different from those of the control except decreased red blood cell, hemoglobin and hematocrit level. Furthermore, plasma IgG2, G3, and G4 isotype distribution was similar between two groups, but IgG1 level was significantly lowered in the TCDD-exposed, indicating a TCDD-mediated functional alteration of B cells. Significantly enhanced level of IgE in plasma, a hallmark of dermal or respiratory allergic response, was also observed in the TCDD-exposed compared with that of the control. Elevated generation of IL-4 and IL-10 was resulted from in vitro stimulation of T cells with PMA plus ionomycin or PHA, respectively, from the TCDD-exposed in comparison to those of the control, suggesting a skewed type-2 response. In addition, the level of IFN${\gamma}$, a multifunctional cytokine for T cell-mediated immunity, was lowered in the TCDD-exposed with upregulation of tumor necrosis factor $\alpha$. The present study suggests that TCDD exposure disturbs immunohomeostasis in humans observed as an aberrant plasma IgE and IgG1 levels and dysregulation of T cell activities.

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비만 및 제2형 당뇨병 쥐 모델에서 과당과 포도당의 섭취가 지방간과 NLRP3 염증조절결합체에 미치는 영향 (Effects of Dietary Fructose and Glucose on Hepatic Steatosis and NLRP3 Inflammasome in a Rodent Model of Obesity and Type 2 Diabetes)

  • 이희재;양수진
    • 한국식품영양과학회지
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    • 제42권10호
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    • pp.1576-1584
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    • 2013
  • 이상의 결과를 종합해 볼 때, 높은 수준의 포도당 섭취는 공복혈당과 공복혈당면적을 높이고 혈중 인슐린 농도와 아티포넥틴의 수준을 낮추어 혈당조절 능력을 억제시켰다. 반면, 높은 수준의 과당 섭취는 인슐린을 요구하지 않는 과당대사의 특이성으로 인해 혈당조절에는 효과적으로 보인다. 그러나 고과당 섭취는 간 조직 및 혈중 중성지방의 농도를 높이고 염증조절복합체 구성단백질의 발현을 조절하여 전염증인자의 발현을 증가시켰다. 이는 간조직에 있어 과당이 포도당보다 높은 수준의 염증반응을 유도하여 NAFLD의 발병과 진행에 보다 유의적인 영향을 준다는 것을 보여준다. 본 연구의 제한점은 일상에서 과당이나 포도당을 단독으로 섭취하는 경우가 드물다는 점과 3주라는 짧은 중재기간에 의한 실험 결과라는 것이다. 앞으로의 연구는 단순당을 장기간 섭취했을 때 혈청과 간 조직을 포함한 다른 대사 관련조직에서 나타나는 변화에 초점을 맞출 필요가 있으며, 염증조절복합체가 염증인자의 발현을 증가시키는 기전을 구체화하는 것이 요구된다.

Synthetic Prion Peptide 106-126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells

  • Song, Kib-Beum;Na, Ji-Young;Oh, Myung-Hoon;Kim, Sok-Ho;Kim, Young-Ha;Park, Byung-Yong;Shin, Gi-Wook;Kim, Bum-Seok;You, Myung-Jo;Kwon, Jung-Kee
    • Toxicological Research
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    • 제28권1호
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    • pp.5-9
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    • 2012
  • It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-$1{\beta}$) and tumor necrosis factor alpha (TNF-${\alpha}$) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

  • Yang, Sungjae;Kim, Yong;Jeong, Deok;Kim, Jun Ho;Kim, Sunggyu;Son, Young-Jin;Yoo, Byong Chul;Jeong, Eun Jeong;Kim, Tae Woong;Han Lee, In-Sook;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • 제24권6호
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    • pp.595-603
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    • 2016
  • (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

Immune Modulation Effect of Pig Placenta Extracts in a Mouse Model: Putative Use as a Functional Food Supplement

  • Park, Hyun-Jung;Suh, Han-Geuk;Kim, Jin-Hoi;Jang, Ae-Ra;Jung, Hyun-Jung;Lee, Sung-Dae;Ha, Woo-Tae;Lee, Ran;Kim, Ji-Hyuk;Kim, Sang-Ho;Sung, Si-Heung;Moon, Sang-Ho;Kim, Bo-Kyung;Song, Hyuk
    • 한국축산식품학회지
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    • 제31권5호
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    • pp.701-709
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    • 2011
  • This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

화장품 소재로서의 흑마늘 추출물에 대한 안전성 평가 -1차 피부자극 실험 및 감작성 중심으로- (Safety Evaluation of Black Garlic Extract for Development of Cosmeceutical Ingredients -Skin irritation and Sensitization Studies-)

  • 이현순;김선희
    • 한국식품영양과학회지
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    • 제39권8호
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    • pp.1213-1219
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    • 2010
  • 본 연구는 흑마늘을 기능성 화장품 소재로 활용하기 위하여 그 기능성을 in vitro에서 tyrosinase 및 elastase 저해 활성을 측정한 결과 피부노화에 관여하는 두 효소의 활성을 모두 저해하였다. 흑마늘 추출물을 hartley계 기니픽 수컷을 사용하여 피부 1차 자극 실험을 실시한 결과 1차 피부자극지수(P.I.I.)가 0.23으로 practically non-irritation(비자극성)에 해당하는 자극으로 피부 자극이 거의 없었음을 알 수 있었다. Maximization test법으로 피부 감작성을 확인한 결과 시험물질에 의한 홍반과 부종 등이 전혀 유발되지 않았다. 이상의 결과로부터 흑마늘 추출물에 대한 기니픽의 피부 감작율은 0%로, 피부에 대한 피부 감작성이 없는 것으로 확인되었다. 따라서 이러한 본 연구의 결과는 흑마늘 추출물이 기능성 화장품 소재로 피부노화를 억제하는 기능성과 안전성확보된 소재임을 추정할 수 있었다.