Details of a Researcher - OGASAWARA Noriko

Papers - OGASAWARA Noriko

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The acid-sensing ion channel 2 (ASIC2) of ciliated cells in the developing rat nasal septum

Shin Kikuchi, Takafumi Ninomiya, Tomoyuki Kawamata, Noriko Ogasawara, Takashi Kojima, Nobutada Tachi, Haruyuki Tatsumi

ARCHIVES OF HISTOLOGY AND CYTOLOGY ( INT SOC HISTOLOGY & CYTOLOGY ) 73 ( 2 ) 81 - 89 2010 [Refereed]

The airway epithelium is exposed to an acidic environment in certain conditions. The acid-sensing ion channel 2 (ASIC2) belongs to the epithelial amiloride-sensitive sodium channel and degenerin (ENaC/DEG) family and is expressed on cilia of the respiratory epithelium. The aim of this study was to detect the expression of ASIC2 in the nasal septum in the embryonic stage of the rat. ASIC2 expression was not observed in the primary cilium but was found in some cilia on embryonic day 17 (E17). After E18, all cilia showed ASIC2 immunoreactivity. RT-PCR analysis revealed that ASIC2b, a subtype of ASIC2, was expressed in the nasal septum while ASIC2a was not. Quantitative Real-time RT-PCR studies indicated that the expression level of ASIC2 mRNA was highest on E21, just before birth. These results imply that ASIC2 plays little part in the development of the nasal septum epithelium. On the other hand, ASIC2, especially ASIC2b, may function for the survival and retention of ciliated cells of the nasal septum against dynamic changes in the pH environment at birth.

DOI PubMed

Expression and localization of tricellulin in human nasal epithelial cells in vivo and in vitro

Tsuyoshi Ohkuni, Takashi Kojima, Noriko Ogasawara, Tomoyuki Masaki, Takafumi Ninomiya, Shin Kikuchi, Mitsuru Go, Ken-ichi Takano, Tetsuo Himi, Norimasa Sawada

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER TOKYO ) 42 ( 4 ) 204 - 211 2009.12 [Refereed]

Tricellulin was identified as the first marker of the tricellular tight junction, which forms at the meeting points of three cells, and it is required for the maintenance of the transepithelial barrier. Although it is also considered to be important for the mucosal barrier of the upper respiratory tract, little is known about its expression and localization. In the present study, we examined the expression and localization of tricellulin in normal human nasal epithelial cells in vivo and in vitro, especially using primary cultures and telomerase reverse transcriptase (hTERT)-transfected cells. In human nasal epithelial cells in vivo and in vitro, mRNA and protein of tricellulin were detected. It was localized not only at tricellular contacts but also at bicellular borders, and in part colocalized with occludin. In human nasal epithelium, by immunoelectron microscopy analysis, tricellulin-associated gold particles were observed around the junction-like structure of the uppermost region. By treatment with 10% fetal bovine serum (FBS), expression of tricellulin mRNA was weakly increased, whereas that of bicellular tight junction molecules was strongly increased, in real-time PCR. These results suggest that tricellulin is stably expressed in human nasal epithelial cells and may play an important role for the sealing of the corner at tricellular contacts to prevent infiltration by various inhaled viruses and antigens.

DOI PubMed

Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells

Ryuta Kamekura, Takashi Kojima, Jun-ichi Koizumi, Noriko Ogasawara, Makoto Kurose, Mitsuru Go, Atsushi Harimaya, Masaki Murata, Satoshi Tanaka, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

CELL AND TISSUE RESEARCH ( SPRINGER ) 338 ( 2 ) 283 - 293 2009.11 [Refereed]

Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin-1 beta and tumor necrosis factor-alpha. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis.

DOI PubMed

Induction of JAM-A during differentiation of human THP-1 dendritic cells

Noriko Ogasawara, Takashi Kojima, Mitsuru Go, Jun Fuchimoto, Ryuta Kamekura, Jun-ichi Koizumi, Tsuyoshi Ohkuni, Tomoyuki Masaki, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 389 ( 3 ) 543 - 549 2009.11 [Refereed]

Junctional adhesion molecule (JAM)-A is not only localized at tight junctions of endothelial and epithelial cells but is also expressed on circulating leukocytes and dendritic cells (DCs). In the present study, to investigate the regulation of JAM-A in DCs, mature DCs were differentiated from the human monocytic cell THP-1 by treatment with IL-4, GM-CSF, TNF-alpha, and ionomycin, and some cells were pretreated with the PPAR-gamma agonists. In the THP-1 monocytes, mRNAs of tight junction molecules, occludin, tricellulin, JAM-A, ZO-1, ZO-2 and claudin-4, -7, -8, and -9 were detected by RT-PCR. In mature DCs that had elongated dendrites, mRNA and protein of JAM-A were significantly increased compared to the monocytes. PPAR-gamma agonists prevented the elongation of dentrites but not upregulation of JAM-A in mature DCs. These findings indicated that the induction of JAM-A Occurred during differentiation of human THP-1 DCs and was independent of PPAR-gamma and the p38 MAPK pathway. (C) 2009 Elsevier Inc. All rights reserved.

DOI PubMed

ヒト鼻粘膜上皮細胞を用いたRSウイルス感染モデルの確立と上皮タイト結合への影響

正木智之, 小島隆, 大國毅, 小笠原徳子, 岡林環樹, 藤井暢弘, 堤裕幸, 澤田典均, 氷見徹夫

日本鼻科学会会誌 ( (一社)日本鼻科学会 ) 48 ( 3 ) 323 - 323 2009.08

ヒト鼻粘膜の機能解析から見えてくること

氷見徹夫, 郷充, 近藤敦, 高野賢一, 正木智之, 小泉純一, 亀倉隆太, 大國毅, 小笠原徳子, 小島隆, 澤田典均

耳鼻咽喉科展望 ( 耳鼻咽喉科展望会 ) 52 ( 補冊1 ) 9 - 18 2009.08

ヒト鼻粘膜上皮の初代培養系を用いたバリア機能の解析は経鼻投与による炎症制御の方法論の確立に重要である。タイト結合はバリア機能に関連し物質の透過性に関与する因子のひとつであり、この機能を調節するメカニズムを解明することは炎症制御に重要である。さらに、樹状細胞やM細胞(micro-folds cell)のような抗原サンプリングに関与する免疫担当細胞の検討は経鼻投与によるアレルギー・感染などの免疫療法の効率化に寄与する。また、タイト結合などの細胞接着に関与する因子はウイルスの受容体であることが示されており、この意味ではウイルス感染の予防のための治療戦略としてタイト結合タンパクの研究を進めることは意義のあることと考えられる。ここでは鼻粘膜上皮と上皮内樹状細胞、さらに鼻粘膜のM細胞の存在について言及し、タイト結合とウイルス感染との関連、さらに、タイト結合タンパクの調節のメカニズムについても言及する。(著者抄録)

What was clarified from a function analysis of the human nasal mucosa?

Tetsuo Himi, Mitsuru Go, Atsushi Kondo, Ken-Ichi Takano, Tomoyuki Masaki, Jun-Ichi Koizumi, Ryuta Kamekura, Atsushi Ohkuni, Noriko Ogasawara, Takashi Kojima, Norimasa Sawada

Oto-Rhino-Laryngology Tokyo 52 ( 1 ) 9 - 18 2009.08

Analysis of the mucosal barrier function using a primary culture system of human nasal mucosal epithelium is important to establish a methodology of inflammation control by the transnasal drug delivery route. Tight junctions are one of the important factors contributing to the permeability of the nasal mucosa to drugs, and it is important to study the factors regulating the nasal mucosal permeability to drugs. Furthermore, examination of the immunocompetence of an individual by sampling cells such as dendritic cells and M cells may be expected to contribute to the establishment of immunotherapy for allergic rhinitis or upper respiratory infections using the transnasal approach. In addition, tight junctions are also known as one of the viral receptors, and it is important for the future to study the characteristics of tight junctions to develop treatment strategies for the prevention of viral infections.

ヒト鼻粘膜上皮細胞と樹状細胞のタイト結合蛋白はthymic stromal lymphopoietin(TSLP)によって誘導される

亀倉隆太, 小島隆, 小笠原徳子, 大國毅, 高野賢一, 郷充, 澤田典均, 氷見徹夫

日本耳鼻咽喉科学会会報 ( (一社)日本耳鼻咽喉科頭頸部外科学会 ) 112 ( 4 ) 376 - 376 2009.04

核内受容体PPAR-γを介したヒト鼻粘膜におけるタイト結合の発現調節機構

小笠原徳子, 小島隆, 郷充, 亀倉隆太, 大國毅, 正木智之, 村田雅樹, 田中敏, 千葉英樹, 氷見徹夫, 澤田典均

日本病理学会会誌 ( (一社)日本病理学会 ) 98 ( 1 ) 323 - 323 2009.03

Lingual hamartoma in a newborn with chromosome 2q terminal deletion

Nobuhiko Seki, Tomoko Shintani, Hiroshi Tsubota, Kazumasa Watanabe, Noriko Ogasawara, Yu-uki Ueda, Tetsuo Himi

International Journal of Pediatric Otorhinolaryngology Extra 3 ( 3 ) 109 - 112 2008.09 [Refereed]

Hamartoma, defined as tumour-like overgrowths of tissue, may occur in any organ in the body and is commonly seen in liver, spleen, kidney and lung, however, lingual hamartoma is a rare entity. Terminal deletion of chromosome 2q is a chromosomal abnormality causing various craniofacial malformations, and no reports can be obtained about patients who have chromosomal disorder presenting with lingual hamartoma. We describe the first case of lingual hamartoma in a patient with terminal deletion of chromosome 2, and summarize the clinical management and the histogenesis of lingual hamartoma from the literature. A 9-month-old girl who had chromosome 2q terminal deletion consulted Sapporo Medical University hospital for evaluation of upper airway obstruction. She had retractive breathing soon after birth and required treatment with continuous positive airway pressure (CPAP). Physical examination showed craniofacial abnormalities, such as round face, high palate, aural atresia, anotia and so on. Fiberoptic examination and CT scan revealed a mass on the right side of the tongue base. She underwent surgical resection and the tumour was pathologically diagnosed as hamartoma. After surgery, her respiratory condition improved to the extent where CPAP was withdrawn. There has been no tumour recurrence during the 1-year follow-up period. © 2007 Elsevier Ireland Ltd. All rights reserved.

DOI

Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation

Jun-ichi Koizumi, Takashi Kojima, Noriko Ogasawara, Ryuta Kamekura, Makoto Kurose, Mitsuru Go, Atsushi Harimaya, Masaki Murata, Makoto Osanai, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

MOLECULAR PHARMACOLOGY ( AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS ) 74 ( 2 ) 432 - 442 2008.08 [Refereed]

The epithelium of upper respiratory tissues such as human nasal mucosa forms a continuous barrier via tight junctions, which is thought to be regulated in part through a protein kinase C (PKC) signaling pathway. To investigate the mechanisms of the regulation of PKC-mediated tight junction barrier function of human nasal epithelium in detail, primary human nasal epithelial cells were treated with the PKC activator 12-O-tetradecanoylophorbol-13-acetate (TPA). In primary human nasal epithelial cells, treatment with TPA led not only to activation of phosphorylation of PKC, myristoylated alanine-rich C kinase substrate, and mitogen-activated protein kinase but also expression of novel PKC-delta, PKC-theta, and PKC-epsilon. Treatment with TPA increased transepithelial electrical resistance, with tight junction barrier function more than 4-fold that of the control, together with up-regulation of tight junction proteins, occludin, zona occludens (ZO)-1, ZO-2 and claudin-1 at the transcriptional level. Furthermore, it affected the subcellular localization of the tight junction proteins and the numbers of tight junction strands. The up-regulation of barrier function and tight junction proteins was prevented by a pan-PKC inhibitor, and the inhibitors of PKC-delta and PKC-theta but not PKC-epsilon. In primary human nasal epithelial cells, transcriptional factors GATA-3 and -6 were detected by reverse transcription-polymerase chain reaction. The knockdown of GATA-3 using RNA interference resulted in inhibition of up-regulation of ZO-1 and ZO-2 by treatment with TPA. These results suggest that TPA-induced PKC signaling enhances the barrier function of human nasal epithelial cells via transcriptional up-regulation of tight junction proteins, and the mechanisms may contribute to a drug delivery system.

DOI PubMed

ヒト鼻粘膜上皮バリアにおけるPKCシグナルを介したタイト結合の調節機構

小島隆, 小泉純一, 小笠原徳子, 亀倉隆太, 黒瀬誠, 今野信宏, 郷充, 高野賢一, 氷見徹夫, 澤田典均

Inflammation and Regeneration ( (一社)日本炎症・再生医学会 ) 28 ( 4 ) 354 - 354 2008.07

Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro

Ken-ichi Takano, Takashi Kojima, Noriko Ogasawara, Mitsuru Go, Shin Kikuchi, Takafumi Ninomiya, Makoto Kurose, Jun-ichi Koizumi, Ryuta Kamekura, Masaki Murata, Satoshi Tanaka, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

JOURNAL OF MOLECULAR HISTOLOGY ( SPRINGER ) 39 ( 3 ) 265 - 273 2008.06 [Refereed]

The human adenoid epithelium forms a continuous barrier against a wide variety of exogenous antigens. In this study, to elucidate the structures of the epithelial barrier in the human adenoid, including M-cells, we identified M-cells using an anti-cytokeratin 20 (Ck20) antibody and investigated expression of tight junction proteins in human adenoid epithelium in vivo and in vitro. In human adenoid epithelium and primary cultures, mRNAs of occludin, junctional adhesion molecule-A, ZO-1, and claudin-1, -4, -7, and -8 were detected by reverse transcription-polymerase chain reaction, whereas claudin-2 and -9 were expressed in vitro. In the epithelium in vivo, some Ck20-positive cells were randomly observed and indicated pocket-like structures, whereas Ck7 was positive in almost cells. Transmission electron microscopy revealed that Ck20-associated gold particles could be identified in M-like cells which had short microvilli and harboured the lymphocyte in the pocket-like structure. In primary cultures in vitro, Ck20-positive cells were also detected and had a function to take up fluorescent microparticles. In Ck20-positive cells in vivo and in vitro, expression of occludin, ZO-1, claudin-1 and -7 were observed at cell borders. These results indicate that the epithelial barrier of the human adenoid is stably maintained by expression of tight junction proteins in the epithelium including Ck20-positive M-like cells.

DOI PubMed

Expression of thymic stromal lymphopoietin (TSLP) in allergic rhinitis : Induction of tight junction proteins in human nasal epithelial cells and dendritic cells by epithelial-derived TSLP

KAMEKURA Ryuta, KOJIMA Takashi, KOIZUMI Jun-ichi, OGASAWARA Noriko, KUROSE Makoto, TAKANO Ken-ichi, GO Mitsuru, HIMI Tetsuo, SAWADA Norimasa

Inflammation and Regeneration ( The Japanese Society of Inflammation and Regeneration ) 28 ( 3 ) 160 - 165 2008.05

Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that triggers dendritic cell (DC)-mediated T helper 2-type inflammatory responses and is considered to be a master switch for allergic inflammation such as that in asthma and atopic dermatitis. Furthermore, proinflammatory cytokines and Toll-like receptor ligands can induce TSLP production in human bronchial epithelial cells and human keratinocytes. We first found high expression of endogenous TSLP in the epithelium of allergic rhinitis with recruitment and infiltration of DCs. In culture, the TSLP production in human nasal epithelial cells was markedly and significantly increased by treatment with the proinflammatory cytokines interleukin 1β/tumor necrosis factor-α and a Toll-like receptor 2 ligand, P₃CSK₄. Since it is also thought that TSLP expression not only activates DCs but also affects the epithelial barrier in allergic rhinitis, we investigated the effects of TSLP on tight junctions of human nasal epithelial cells and DCs in vitro. Treatment with TSLP enhanced the barrier function of human nasal epithelial cells in vitro together with an increase of the tight junction proteins claudin-1,-4,-7, and occludin. Furthermore, TSLP could exclusively induce claudin-7 expression in mouse DC line XS52, which expressed tight junction molecules claudin-1,-3,-4,-6,-7,-8, occludin and tricellulin.
These findings suggest that nasal epithelial-derived TSLP plays an important role in allergic rhinitis as well as asthma and atopic dermatitis and may control tight junctions of epithelial cells and DCs to preserve the epithelial barrier and promote direct sampling of antigens by DCs.

DOI CiNii

当科における副咽頭間隙悪性腫瘍症例の検討、及びアプローチ法としてのmaxillary swingの経験

坪田大, 郷充, 金泉悦子, 関伸彦, 小笠原徳子, 新谷朋子, 氷見徹夫

頭頸部癌 ( (一社)日本頭頸部癌学会 ) 34 ( 2 ) 212 - 212 2008.05

ヒト鼻粘膜上皮バリアにおけるPKCシグナルを介したタイト結合の調節機構

小泉純一, 小島隆, 黒瀬誠, 亀倉隆太, 小笠原徳子, 今野信宏, 郷充, 澤田典均, 氷見徹夫

日本鼻科学会会誌 ( (一社)日本鼻科学会 ) 46 ( 3 ) 263 - 263 2007.08

中耳結核の3症例

小笠原徳子, 新谷朋子, 関伸彦, 金泉悦子, 坪田大, 氷見徹夫

耳鼻咽喉科臨床補冊 ( 耳鼻咽喉科臨床学会 ) ( 補冊120 ) 55 - 55 2007.07

テロメラーゼ遺伝子導入培養ヒト鼻粘膜上皮細胞のタイト結合の発現と機能

小島隆, 黒瀬誠, 亀倉隆太, 小泉純一, 小笠原徳子, 氷見徹夫, 澤田典均

Inflammation and Regeneration ( (一社)日本炎症・再生医学会 ) 27 ( 4 ) 439 - 439 2007.07

Angioleiomyoma of the left subcutaneous external nose

Noriko Ogasawara, Hiroshi Tsubota, Tomoko Shintani, Masako Watanabe, Kazumasa Watanabe, Nobuhiko Seki, Tetsuo Himi

Practica Oto-Rhino-Laryngologica ( Society of Practical Otolaryngology ) 100 ( 9 ) 709 - 713 2007 [Refereed]

Angioleiomyoma is a benign tumor composed of smooth muscle cells and vascular endothelial cells, which is most commonly found in the uterus, skin, and alimentary canal as a painful mass. In the head and neck region, the incidence of this tumor is rare and pain is usually absent. We report a rare case of angioleiomyoma occurring in the left subcutaneous extrernal nose. A 41-year-old man visited our hospital complaining of a swelling on the left side of the nose. Physical examination revealed a soft mass in the left subcutaneous extrernal nose. CT scan and MRI with gadolinium enhancement showed well-enhanced mass in the left subcutaneous extrernal nose without bone destruction or apparent invasion into the left nasal cavity. Aspiration biopsy cytology revealed blood only. The tumor was fully excised without major intraoperative bleeding, and the postoperative course was successful. Immunohistochemical study revealed postive staining for vimentin and α-smooth muscle actin in tumor cells, and the tumor was diagnosed as angioleiomyoma. For over a year following surgery, there has been no evidence of recurrence.

DOI

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Papers - OGASAWARA Noriko