Details of a Researcher - KAMEKURA Ryuta

Papers - KAMEKURA Ryuta

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Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappa B in dendritic cells

Ryuta Kamekura, Takashi Kojima, Akira Takashima, Jun-ichi Koizumi, Noriko Ogasawara, Mitsuru Go, Ken-ichi Takano, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

HISTOCHEMISTRY AND CELL BIOLOGY ( SPRINGER ) 133 ( 3 ) 339 - 348 2010.03 [Refereed]

Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell (DC)-mediated Th2-type inflammatory responses. The activated DCs can penetrate the epithelium to directly take up antigen without compromising the barrier function. Although it is reported that DCs express tight junction molecules and can establish tight junction-like structures with adjacent epithelial cells to preserve the epithelial barrier, the regulation of expression of tight junction molecules in DCs remains unknown. In the present study, to investigate the mechanical regulation of expression of tight junction molecules in DCs, XS52 DCs that was a long-term DC line established from the epidermis of a newborn BALB/c mouse, were treated with TSLP or toll-like receptor (TLR) ligands. In XS52 cells, tight junction molecules claudin-1, -3, -4, -6, -7, -8, and occludin were detected. mRNA expression of TSLP receptor and all these tight junction molecules was significantly increased in activated XS52 cells after treatment with TSLP. In addition, expression of claudin-7 protein was increased in dose- and time-dependent manner. In XS52 cells, which express TLR2, TLR3, TLR4, and TLR7, but not TLR9, expression of claudin-7 protein was also increased after treatment with ligands of TLR2, TLR4 or TLR7/8, Pam(3)Cys-Ser-(Lys)(4), LPS, or CL097. The NF-kappa B inhibitor IMD-0354 prevented upregulation of claudin-7 after treatment with TSLP or TLR ligands. These findings indicate that TSLP induces expression of tight junction protein claudin-7 in DCs via NF-kappa B as well as via TLRs and may control tight junctions of DCs to preserve the epithelial barrier during allergic inflammation.

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

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

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

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

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

アレルギー性鼻炎における鼻粘膜上皮バリアと免疫調節機構

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

アレルギーの臨床 ( (株)北隆館 ) 27 ( 13 ) 1038 - 1043 2007.12

鼻粘膜上皮は機械的バリアだけでなく、「粘膜免疫機構」という自然免疫・獲得免疫を成立させるための重要な「免疫臓器」であることが次々と明らかとなっている。鼻粘膜においてもタイト結合と樹状細胞との関係は、古典的な抗原感知・移送という概念とは異なる新しい抗原サンプリング機構のあることがわかった。さらに、アレルギー性鼻炎では、アレルギー発症に関与する重要なサイトカインであるTSLPが主に上皮に強く発現していることが確認され、鼻粘膜上皮がアレルギー調節機構を持つ細胞群として重要であることが考えられた。(著者抄録)

Induction of claudins in passaged hTERT-transfected human nasal epithelial cells with an extended life span

Makoto Kurose, Takashi Kojima, Jun-Ichi Koizumi, Ryuta Kamekura, Takafumi Ninomiya, Masaki Murata, Shingo Ichimiya, Makoto Osanai, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

CELL AND TISSUE RESEARCH ( SPRINGER ) 330 ( 1 ) 63 - 74 2007.10 [Refereed]

The epithelial barrier of the upper respiratory tract, such as that of the nasal mucosa, plays a crucial role in host defense. The epithelial barrier is regulated in large part by the apical-most intercellular junctions, referred to as tight junctions. However, the mechanisms regulating of tight junction barrier in human nasal epithelial cells remain unclear because the proliferation and storage of epithelial cells in primary cultures are limited. In the present study, we introduced the catalytic component of telomerase, the hTERT gene, into primary cultured human nasal epithelial cells and examined the properties of the transfectants, including their expression of tight junctions, compared with primary cultures. The ectopic expression of hTERT in the epithelial cells resulted in adequate growth potential and a longer lifespan of the cells. The properties of the passaged hTERT-transfected cells including tight junctions were similar to those of the cells in primary cultures. The barrier function in the transfectants after treatment with 10% FBS was significantly enhanced with increases of integral tight junction proteins claudin-1 and -4. When the transfectants were treated with TGF-beta, which is assosciated with nasal polyposis and chronic rhinosinusitis, upregulation of only claudin-4 was observed, without a change of barrier function. In human nasal epithelial cells, the claudins may be important for barrier function and a novel target for a drug-delivery system. Our results indicate that hTERT-transfected human nasal epithelial cells with an extended lifespan can be used as an indispensable and stable model for studying the regulation of claudins in human nasal epithelium.

DOI PubMed

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

Connexin 26 expression prevents down-regulation of barrier and fence functions of tight junctions by Na+/K+-ATPase inhibitor ouabain in human airway epithelial cell line Calu-3.

Go M, Kojima T, Takano K, Murata M, Koizumi J, Kurose M, Kamekura R, Osanai M, Chiba H, Spray DC, Himi T, Sawada N

Experimental cell research ( 19 ) 312 3847 - 3856 2006.11 [Refereed]

DOI PubMed

in vivoおよびin vitroにおけるヒト鼻粘膜上皮細胞のM様細胞とタイト結合

小泉純一, 小島隆, 黒瀬誠, 高野賢一, 亀倉隆太, 澤田典均, 氷見徹夫

耳鼻咽喉科免疫アレルギー ( 日本耳鼻咽喉科免疫アレルギー学会 ) 24 ( 2 ) 179 - 179 2006.09

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