研究者詳細 - 前田　恵

Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos. 査読国際誌

Matsuzaki H, Kumagai-Takei N, Lee S, Maeda M, Sada N, Hatayama T, Yamamoto S, Ikeda M, Yoshitome K, Min Y, Nishimura Y, Otsuki T

Environmental health and preventive medicine 22 ( 1 ) 53 - 53 2017年6月

Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. 査読国際誌

Maeda M, Chen Y, Lee S, Kumagai-Takei N, Yoshitome K, Matsuzaki H, Yamamoto S, Hatayama T, Ikeda M, Nishimura Y, Otsuki T

International journal of oncology 50 ( 6 ) 2024 - 2032 2017年6月

Molecular characterization of tomato α1,3/4-fucosidase, a member of glycosyl hydrolase family 29 involved in the degradation of plant complex type N-glycans 査読国際誌

Md. Ziaur Rahman, Megumi Maeda, Satsuki Itano, Md. Anowar Hossain, Takeshi Ishimizu, Yoshinobu Kimura

Journal of Biochemistry 161 ( 5 ) 421 - 432 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press

In this study, we identified a gene in tomato that encodes an acidic α-fucosidase (LOC101254568 or Solyc03g006980, α-Fuc'ase S1-1), which may be involved in the turnover of plant complex-type N-glycans. Recombinant α-Fuc'ase S1-1 (rFuc'ase S1-1) was expressed using a baculovirus-insect cell expression system. rFuc'ase Sl-1 is 55 kDa in size and has an optimum pH around 4.5. It substantially hydrolyzed the non-reducing terminal α1,3-fucose residue on LNFP III and α1,4-fucose residues of Lea epitopes on plant complex-type N-glycans, but not the α1,2-fucose residue on LNFP I or the α1,3-fucose residue on pyridylaminated Fucα1-3GlcNAc. Furthermore, we found that this tomato α-Fuc'ase S1-1 was inactive toward the core penta-oligosaccharide unit [Manβ1-4(Xylβ1-2)GlcNAcβ1-4(Fucα1-3)GlcNAc-PA] of plant complex-type N-glycans. Molecular 3D modelling of α-Fuc'ase Sl-1 and structure/sequence interpretation based on comparison with a homologous a-fucosidase from Bifidobacterium longum subsp. infantis (Blon-2336) indicated that residues Asp193 and Glu237 might be important for substrate binding.

DOI： 10.1093/jb/mvw089

アスベスト長期曝露ヒト制御性T細胞株モデルにおける細胞周期の解析

大槻剛巳, 李順姫, 松崎秀紀, 武井直子, 吉留敬, 西村泰光, 前田恵

産業衛生学雑誌 59 ( 臨増 ) 505 - 505 2017年5月

Occurrence of complex type free N-glycans with a single GlcNAc residue at the reducing termini in the fresh-water plant, Egeria densa 査読国際誌

Megumi Maeda, Natsuki Ebara, Misato Tani, Christopher J. Vavricka, Yoshinobu Kimura

Glycoconjugate Journal 34 ( 2 ) 229 - 240 2017年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer New York LLC

In our previous study, we found unique free N-glycans (FNGs), which carry a single GlcNAc residue (GN1) at the reducing-end side and the Lewis-a epitope at the non-reducing-end side, in the culture broth of rice cells. Based on the FNG structural features and the substrate specificity of plant ENGase, we hypothesized that there might be a novel biosynthetic mechanism responsible for the production of these unique GN1-FNGs, in which high-mannose type (HMT)-GN1-FNGs produced in the cytosol from misfolded glycoproteins by ENGase are transported back into the endoplasmic reticulum and processed to plant complex type (PCT)-GN1-FNGs in the Golgi apparatus. Until now, however, PCT-GN1-FNGs had only been found in the culture broth of rice cultured cells and never in plants, suggesting that the formation of PCT-GN1-FNGs might be generated under special or artificial conditions. In this study, we confirm the presence of PCT-GN1-FNGs, HMT-GN1-FNGs and PCT-GN2-FNGs in the fresh-water plant Egeria densa. These results suggest that a mechanism responsible for the production of PCT-GN1-FNG is present in native plant tissues.

DOI： 10.1007/s10719-016-9758-z

Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers. 査読国際誌

Lee S, Matsuzaki H, Maeda M, Yamamoto S, Kumagai-Takei N, Hatayama T, Ikeda M, Yoshitome K, Nishimura Y, Otsuki T

International journal of oncology 50 ( 1 ) 66 - 74 2017年1月

Structural feature of N-glycans of bamboo shoot glycoproteins: useful source of plant antigenic N-glycans 査読国際誌

Chinatsu Tanabe, Kaori Furuta, Megumi Maeda, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 81 ( 7 ) 1405 - 1408 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

An effective method to prepare plant complex type (PCT) N-glycans in large amounts has been required to evaluate their immunological activity. In this study, we found that glycoproteins in bamboo shoots predominantly carry PCT N-glycans including the Lewis a epitope-containing ones, suggesting that bamboo shoot is an excellent source for the plant antigenic glycans to synthesize immunoactive neoglycopolymers.

DOI： 10.1080/09168451.2017.1320519

Web of Science

ヒトT細胞株への白石綿・青石綿継続曝露に伴う細胞特性の変化査読

李順姫, 前田恵, 松﨑秀紀, 武井直子, 山本祥子, 幡山圭代, 吉留敬, 西村泰光, 大槻剛巳

日本予防医学雑誌 10 ( 3 ) 119 - 125 2016年12月

健康増進住居環境の構築：マイナス帯電粒子優位室内環境によるナチュラル・キラー活性の増強査読

西村泰光, 高橋一聡, 小谷宗男, 間瀬昭則, 白濱毅, 前田恵, 李順姫, 松崎秀紀, 武井直子, 吉留敬, 阿見和久, 大槻剛巳

生存科学 26 ( 2 ) 181 - 190 2016年10月

珪酸粒子・アスベスト繊維の免疫影響査読

大槻剛巳, 李順姫, 前田恵, 林宏明, 松﨑秀紀, 武井直子, 吉留敬, 西村泰光

繊維状物質研究 3 4 - 11 2016年10月

FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line. 査読国際誌

Matsuzaki H, Lee S, Maeda M, Kumagai-Takei N, Nishimura Y, Otsuki T

Journal of immunotoxicology 13 ( 5 ) 620 - 7 2016年9月

Possible contribution of alpha2,6-sialylation to luteolysis in cows by inhibiting the luteotropic effects of galectin-1 査読国際誌

Kazuhisa Hashiba, Junko Nio-Kobayashi, Masahiro Sano, Megumi Maeda, Yoshinobu Kimura, Yuki Yamamoto, Koji Kimura, Kiyoshi Okuda

Biology of Reproduction 95 ( 1 ) 17 - 17 2016年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Society for the Study of Reproduction

The corpus luteum (CL) is essential for establishing pregnancy. If pregnancy does not occur during the estrous cycle, luteolysis is induced by prostaglandin (PG) F2alpha secreted from the uterus. Galectin-1, a beta-galactose-binding protein, is expressed in the functional CL of cows and increases the viability of bovine luteal steroidogenic cells (LSCs) by modifying the functions of membrane glycoproteins. The binding of galectin-1 to glycoproteins is blocked by alpha2,6-sialylation of the terminal galactose residues of glycoconjugates, which is catalyzed by a sialyltransferase (ST6Gal-I). However, the physiological role of alpha2,6-sialic acid in bovine CL is unclear. The level of alpha2,6-sialylation of the bovine CL was higher during the regressed-luteal stage than in other luteal stages. Lectin histochemistry revealed that alpha2,6-sialylated glycoconjugates were localized to luteal endothelial cells throughout the estrous cycle. In addition, alpha2,6-sialylated glycoconjugates concentrated to the membrane of LSCs during the regressed-luteal stage. PGF2alpha treatment for 72 h enhanced the expression of ST6Gal-I mRNA and the level of alpha2,6-sialylated glycoproteins in mid-LSCs. The level of alpha2,6-sialylated glycoproteins of late-stage LSCs (Days 15-17 after ovulation) was higher than that of mid-stage LSCs (Days 8-12 after ovulation), and galectin-1 increased the viability of mid-LSCs but not that of late-stage LSCs. Furthermore, galectin-1 increased the viability of late-LSCs when alpha2,6-sialic acid residues were removed by neuraminidase. The overall findings suggest that alpha2,6-sialylation stimulated by PGF2alpha contributes to luteolysis by inhibiting the luteotropic effects of galectin-1 in bovine CL.

DOI： 10.1095/biolreprod.116.140194

The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells. 査読国際誌

Yuho Maki, Yasumitsu Nishimura, Shinichi Toyooka, Junichi Soh, Kazunori Tsukuda, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoka, Tsuyoshi Ueno, Norimitsu Tanaka, Hiromasa Yamamoto, Hiroaki Asano, Megumi Maeda, Naoko Kumagai-Takei, Suni Lee, Hidenori Matsuzaki, Takemi Otsuki, Shinichiro Miyoshi

Oncology letters 11 ( 5 ) 3308 - 3316 2016年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.

DOI： 10.3892/ol.2016.4412

Rice alpha-fucosidase active against plant complex type N-glycans containing Lewis a epitope: purification and characterization 査読国際誌

Md. Ziaur Rahman, Makoto Fujishige, Megumi Maeda, Yoshinobu Kimura

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 ( 2 ) 291 - 294 2016年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS LTD

Rice -fucosidase (-fucosidase Os, 58kDa) that is active for 1-4 fucosyl linkage in Lewis a unit of plant N-glycans was purified to homogeneity. -fucosidase Os showed activity against 1-3 fucosyl linkage in Lacto-N-fucopentaose III but not 1-3 fucosyl linkage in the core of plant N-glycans. The N-terminal sequence of -fucosidase Os was identified as A-A-P-T-P-P-P-L-, and this sequence was found in the amino acid sequence of the putative rice -fucosidase 1 (Os04g0560400).

DOI： 10.1080/09168451.2015.1079479

Web of Science

Structural features of N-glycans linked to glycoproteins expressed in three kinds of water plants: Predominant occurrence of the plant complex type N-glycans bearing Lewis a epitope 査読国際誌

Megumi Maeda, Misato Tani, Takeo Yoshiie, Christopher J. Vavricka, Yoshinobu Kimura

Carbohydrate Research 435 50 - 57 2016年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier Ltd

The Japanese cedar pollen allergen (Cry j1) and the mountain cedar pollen allergen (Jun a1) are glycosylated with plant complex type N-glycans bearing Lewis a epitope(s) (Galβ1-3[Fucα1-4]GlcNAc-). The biological significance of Lewis a type plant N-glycans and their effects on the human immune system remain to be elucidated. Since a substantial amount of such plant specific N-glycans are required to evaluate immunological activity, we have searched for good plant-glycan sources to characterize Lewis a epitope-containing plant N-glycans. In this study, we have found that three water plants, Elodea nuttallii, Egeria densa, and Ceratophyllum demersum, produce glycoproteins bearing Lewis a units. Structural analysis of the N-glycans revealed that almost all glycoproteins expressed in these three water plants predominantly carry plant complex type N-glycans including the Lewis a type, suggesting that these water plants are good sources for preparation of Lewis a type plant N-glycans in substantial amounts.

DOI： 10.1016/j.carres.2016.09.008

ウシ黄体維持機構におけるepidermal growth factor receptorのcore fucosylationの役割

羽柴一久, 小林純子, 佐野栄宏, 前田恵, 木村吉伸, 奥田潔, 木村康二

日本繁殖生物学会講演要旨集 109 OR2-33 - OR2-33 2016年

記述言語：日本語出版者・発行元：公益社団法人日本繁殖生物学会

【目的】Epidermal growth factor receptor（EGFR）に結合するN型糖鎖上のcore fucoseは，epidermal growth factor（EGF）のEGFRへの結合に重要である。EGFは黄体細胞の生存を維持し，EGFRへの結合親和性は機能黄体において高いことから，黄体においてもEGFRの黄体維持作用にcore fucosylationの関与が考えられる。本研究では，1）発情周期を通じたウシ黄体のcore fucosylationレベルとfucose含有糖タンパク質の局在，2）黄体細胞のEGFR糖鎖のcore fucosylationの有無，3） EGFの黄体機能維持作用に及ぼすcore fucosylationの影響を検討した。【方法】1）発情周期を通じた黄体（初期：Days 2–3，形成期：Days 5–6，中期Days 8–12，後期：Days 15–17，退行期：Days 19–21）の膜画分のcore fucosylationレベルをfucoseを認識するAALレクチンを用いて検討し，fucose含有糖タンパク質の局在を解析した。2）中期黄体細胞から免疫沈降法によりEGFRタンパク質を回収後，core fucosylationの有無を調べた。3）中期黄体細胞にα-fucosidase（0.01，0.1 units/ml）を添加してcore fucoseを切断し，16時間後のcore fucosylationレベル，上清中のprogesterone（P4）濃度と生存率を検討した。黄体細胞にα-fucosidase（0.1 units/ml）とEGF（5，10 ng/ml）を単独又は組み合わせて添加し，24時間後のP4濃度と生存率を調べた。【結果】1）黄体の糖タンパク質のcore fucosylationレベルは後期，退行期と比較して，初期，形成期と中期に高く，fucose含有糖タンパク質は黄体細胞に局在した。2）黄体細胞のEGFR糖鎖はcore fucosylationを受けていた。3）黄体細胞の糖タンパク質のcore fucosylationレベルと生存率は，α-fucosidase添加区において減少し，P4産生に変化はなかった。EGFによる生存率の増加は，α-fucosidaseの共添加により減少し，P4産生に変化はなかった。以上より，EGFの黄体機能維持作用にEGFRのcore fucosylationが重要であり，core fucosylationの低下が黄体の構造的退行に関与する可能性が示された。

DOI： 10.14882/jrds.109.0_or2-33

CiNii Article

Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos. 査読国際誌

Ying C, Maeda M, Nishimura Y, Kumagai-Takei N, Hayashi H, Matsuzaki H, Lee S, Yoshitome K, Yamamoto S, Hatayama T, Otsuki T

Toxicology 338 86 - 94 2015年12月

Exposure to negatively charged-particle dominant air-conditions on human lymphocytes in vitro activates immunological responses. 査読国際誌

Nishimura Y, Takahashi K, Mase A, Kotani M, Ami K, Maeda M, Shirahama T, Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Otsuki T

Immunobiology 220 ( 12 ) 1359 - 68 2015年12月

T cell alteration caused by exposure to asbestos 査読

Megumi Maeda, Shoko Yamamoto, Tamayo Hatayama, Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Yasumitsu Nishimura, Yoshinobu Kimura, Takemi Otsuki

Biological Effects of Fibrous and Particulate Substances 195 - 210 2015年10月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

A model to examine the effects of continuous exposure to asbestos on human T cells was established to interpret experimental findings for clinical utilization. Although transient exposure causes apoptosis in the human polyclonal cell line MT-2, continuous and relatively low-dose exposure resulted in resistance against asbestos-induced apoptosis with a higher production of TGF-β and IL-10 and subsequent resistance to TGF-β-induced growth inhibition and activation of STAT3 and Bcl-2. These alterations caused by continuous exposure to chrysotile asbestos were also observed in a subline exposed continuously to crocidolite and included resistance to apoptosis, changes of cytokine production, and demonstration of the importance of Bcl-2 for resistance against apoptosis. In addition, analysis of protein expression among the MT-2 original cell line, which was never exposed to asbestos, and the continuously exposed subline showed the phosphorylation of β-actin and the increasing level of cytoskeletal molecules. These findings indicate the importance of the cytoskeleton as the initial contact site between cells and asbestos fibers, particularly fibers that cannot move into the inside of cells because of their physical features. Finally, the CXCR3 chemokine receptor and related antitumor cytokine IFN-γ were assayed in these sublines continuously exposed to asbestos, as well as in vitro stimulated freshly isolated peripheral CD4 T cells derived from healthy donors and exposed to asbestos fibers. The CXCR3 expression and production capacity for IFN-γ were reduced by asbestos exposure, and these findings were also confirmed for peripheral CD4 T cells derived from patients with pleural plaque and malignant mesothelioma. The overall findings observed in continuously exposed human T cell models will contribute towards the early detection of asbestos exposure and occurrence of mesothelioma using peripheral blood and will improve the immune status (reducing antitumor immunity in asbestos-exposed patients) through the use of certain physiological substances derived from plants, foods, and microorganisms.

DOI： 10.1007/978-4-431-55732-6_11