Regulation of human nasal mucosal barrier by tight junctions via innate immunity

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: KOJIMA Takashi Sapporo Medical University, 医学部, 准教授 (30260764)
• Co-Investigator(Kenkyū-buntansha): TANAKA Satoshi 札幌医科大学, 医学部, 講師 (30374250) ; MURATA Masaki 札幌医科大学, 医学部, 助教 (10404592) ; MASAKI Tomoyuki 札幌医科大学, 医学部, 研究員 (30457717)
• Project Period (FY): 2008 – 2010
• Keywords: 自然免疫 / タイト結合 / TLR / RSウィルス / ヒト鼻粘膜 / シグナル伝達

Research Abstract

In the present study, we investigated the regulation of human nasal mucosal barrier by tight junctions in the nasal epithelial cells and dendritic cells to prevent and therapy for infections and allergy. TSLP (high-expression in allergic rhinitis), TLR3 (association with innate immunity), PPAR-gamma (nuclear hormone receptor) and RSV (infection in human airway) affected the barrier by tight junctions via distinct signal transduction pathways including PKC.

Research Products

• [Journal Article] Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids. (2011)
  • Author(s): Masaki T, Fuchimoto J, Obata K, Kurose M, Shintani T, Sawada N, Himi T
  • Journal Title: Acta Otolaryngol 131 Pages: 116-123
  • Peer Reviewed
• [Journal Article] Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-α via distinct NF-κB pathways in human nasal epithelial cells. (2011)
  • Author(s): Ohkuni T, Kojima T, Ogasawara N, Masaki T, Fuchimoto J, Kamekura R, Koizumi JI, Ichimiya S, Murata M, Tanaka S, Himi T, Sawada N
  • Journal Title: Toxicol Appl Pharmacol. 250 Pages: 29-38
  • Peer Reviewed
• [Journal Article] c-Jun N-terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells. (2010)
  • Author(s): Kojima T, Fuchimoto J, Yamaguchi H, Ito T, Takasawa A, Ninomiya T, Kikuchi S, Ogasawara N, Ohkuni T, Masaki T, Hirata K, Himi T, Sawada N
  • Journal Title: J Cell Physiol 225 Pages: 720-733
  • Peer Reviewed
• [Journal Article] Tricellulin is expressed in autotypic tight junctions of peripheral myelinating schwann cells. (2010)
  • Author(s): Kikuchi S, Ninomiya T, Tatsumi H, Sawada N, Kojima T
  • Journal Title: J Histochem Cytochem 58 Pages: 1067-1073
• [Journal Article] Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-κB in dendritic cells. (2010)
  • Author(s): Kamekura R, Kojima T, Takashima A, Koizumi JI, Ogasawara N, Go M, Takano KI, Murata M, Tanaka S, Ichimiya S, Himi T, Sawada N
  • Journal Title: Histochem Cell Biol 133 Pages: 339-348
  • Peer Reviewed
• [Journal Article] Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. (2010)
  • Author(s): Sawada K, Ariki S, Kojima T, Saito A, Yamazoe M, Nishitani C, Shimizu T, Takahashi M, Mitsuzawa H, Yokota SI, Sawada N, Fujii N, Takahashi H, Kuroki Y.
  • Journal Title: J Biol Chem 285 Pages: 8434-8443
  • Peer Reviewed
• [Journal Article] PPARγ agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells. (2010)
  • Author(s): Ogasawara N, Kojima T, Go M, Ohkuni T, Koizumi J, Kamekura R, Masaki T, Murata M, Tanaka S, Fuchimoto J, Himi T, Sawada N
  • Journal Title: Pharmacol Res 61 Pages: 489-498
  • Peer Reviewed
• [Journal Article] Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase-transfected human pancreatic duct epithelial cells. (2010)
  • Author(s): Yamaguchi H, Kojima T, Ito T, Kimura Y, Imamura M, Son S, Koizumi J, Murata M, Nagayama M, Nobuoka T, Tanaka S, Hirata K, Sawada N
  • Journal Title: Am J Pathol 177 Pages: 698-712
  • Peer Reviewed
• [Journal Article] RSウィルス感染症と喘鳴・喘息 (2010)
  • Author(s): 堤裕幸, 平川賢史, 正木智之, 氷見徹夫, 岡林環樹, 横田伸一, 藤井暢弘, 小島隆, 澤田典均
  • Journal Title: 小児耳鼻咽喉科 31(3) Pages: 248-252
• [Journal Article] Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells. (2009)
  • Author(s): Son S, Kojima T, Decaens C, Yamaguchi H, Ito T, Imamura M, Murata M, Tanaka S, Chiba H, Hirata K, Sawada N
  • Journal Title: Histochem Cell Biol 131 Pages: 411-424
  • Peer Reviewed
• [Journal Article] Impaired cutaneous wound healing in mice lacking tetranectin. (2009)
  • Author(s): Iba K, Hatakeyama N, Kojima T, Murata M, Matsumura T, Wewer UM, Wada T, Sawada N, Yamashita T.
  • Journal Title: Wound Repair Regen 17 Pages: 108-112
  • Peer Reviewed
• [Journal Article] Thymic stromal lymphopoietin enhances tight junction barrier function of human nasal epithelial cells. (2009)
  • Author(s): Kamekura R, Kojima T, Koizumi J, Ogasawara N, Kurose M, Go M, Harimaya A, Murata M, Tanaka S, Chiba H, Himi T, Sawada N
  • Journal Title: Cell Tissue Res 338 Pages: 283-293
  • Peer Reviewed
• [Journal Article] Expression and localization of tricellulin in human nasal epithelial cells in vivo and in vitro. (2009)
  • Author(s): Ohkuni T, Kojima T, Ogasawara N, Masaki T, Ninomiya T, Kikuchi S, Go M, Takano K, Himi T, Sawada N
  • Journal Title: Med Mol Morphol 42 Pages: 204-211
  • Peer Reviewed
• [Journal Article] Induction of JAM-A during differentiation of human THP-1 dendritic cells. (2009)
  • Author(s): Ogasawara N, Kojima T, Go M, Fuchimoto J, Kamekura R, Koizumi J, Ohkuni T, Masaki T, Murata M, Tanaka S, Ichimiya S, Himi T, Sawada N
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 543-549
  • Peer Reviewed
• [Journal Article] Tight junction proteins and signal transduction pathways in hepatocytes. (2009)
  • Author(s): Kojima T, Murata M, Yamamoto T, Lan M, Imamura M, Son S, Takano K-i, Yamaguchi H, Ito T, Tanaka S, Chiba H, Hirata K, Sawada N
  • Journal Title: Histol Histopathol 24 Pages: 1463-1472
  • Peer Reviewed
• [Journal Article] ヒト鼻粘膜の機能解析から見えてくること (2009)
  • Author(s): 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
  • Journal Title: 耳鼻咽喉科展望 52 Pages: 9-18
• [Journal Article] 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. (2008)
  • Author(s): Kamekura R, Kojima T, Koizumi J, Ogasawara N, Kurose M, Takano K, Go M, Himi T, Sawada N
  • Journal Title: Inflammation and Regeneration 28 Pages: 160-165
• [Journal Article] Transforming growth factor-β induces epithelial to mesenchymal transition by down-regulation of claudin-1 expression and the fence function in adult rat hepatocytes. (2008)
  • Author(s): Kojima T, Takano K, Yamamoto T, Imamura M, Murata M, Son S, Yamaguchi H, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: Liver Int 28 Pages: 534-545
  • Peer Reviewed
• [Journal Article] Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro. (2008)
  • Author(s): Takano K, Kojima T, Ogasawara N, Go M, Kikuchi S, Ninomiya T, Kurose M, Koizumi J, Kamekura R, Murata M, Tanaka S, Chiba H, Himi T, Sawada N
  • Journal Title: J Mol Histol 39(3) Pages: 265-273
  • Peer Reviewed
• [Journal Article] Tight junction proteins claudin-2 and-12 are critical for vitamin D-dependent Ca^<2+> absorption between enterocytes. (2008)
  • Author(s): Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, Yamashita T, Kato S, Sawada N, Chiba H.
  • Journal Title: Mol Biol Cell 19 Pages: 1912-1921
  • Peer Reviewed
• [Journal Article] Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation. (2008)
  • Author(s): Koizumi J, Kojima T, Ogasawara N, Kamekura R, Kurose M, Go M, Harimaya A, Murata M, Osanai M, Chiba H, Himi T, Sawada N
  • Journal Title: Mol Pharmacol 74 Pages: 432-442
  • Peer Reviewed
• [Journal Article] Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy. (2008)
  • Author(s): Nishikiori N, Osanai M, Chiba H, Kojima T, Inatomi S, Ohguro H, Sawada N
  • Journal Title: Clinical Ophthalmology 2 Pages: 233-235
  • Peer Reviewed
• [Journal Article] IGF-I regulates tight-junction protein claudin-1 during differentiation of osteoblast-like MC3T3-E1 cells via a MAP-kinase pathway. (2008)
  • Author(s): Hatakeyama N, Kojima T, Iba K, Murata M, Thi MM, Spray DC, Osanai M, Chiba H, Ishiai S, Yamashita T, Sawada N
  • Journal Title: Cell Tissue Res 334 Pages: 243-254
  • Peer Reviewed
• [Journal Article] 粘膜のバリアと抗原サンプリング-鼻粘膜を介した新たな治療戦略にむけて- (2008)
  • Author(s): 郷充, 小島隆, 亀倉隆太, 小笠原徳子, 小泉純一, 黒瀬誠, 高野賢一, 澤田典均, 氷見徹夫
  • Journal Title: 耳鼻咽喉科展望 51 Pages: 32-38
• [Journal Article] An NF-κB signaling pathway via PKCδ regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells.
  • Author(s): Masaki T, Kojima T, Okabayashi T, Ogasawara N, Ohkuni T, Obata K, Takasawa A, Murata M, Tanaka S, Hirakawa S, Fuchimoto J, Ninomiya T, Fujii N, Tsutsumi H, Himi T, Sawada N
  • Journal Title: Mol Biol Cell in press
  • Peer Reviewed
• [Journal Article] Effects of Clostridium perfringens enterotoxin via claudin-4 on normal human pancreatic duct epithelial cells and cancer cells.
  • Author(s): Yamaguchi H, Kojima T, Ito T, Kyuno D, Kimura Y, Imamura M, Hirata K, Sawada N
  • Journal Title: Cell Mol Biol Lett in press
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of claudin-18 via specific protein kinase C signaling pathways and modification of DNA-methylation in human pancreatic cancer cells.
  • Author(s): Ito T, Kojima T, Yamaguchi H, Kyuno D, Kimura Y, Imamura M, Takasawa A, Murata M, Tanaka S, Hirata K, Sawada N
  • Journal Title: J Cell Biochem in press
  • Peer Reviewed
• [Journal Article] Expression and function of claudins in hepatocytes. CLAUDINS : METHODS AND PROTOCOLS.
  • Author(s): 小島隆, 澤田典均
  • Journal Title: Methods in Molecular Biology in press
  • Peer Reviewed
• [Journal Article] Altered expression of claudin-1, claudin-7, and tricellulin regardless of human papilloma virus infection in human tonsillar squamous cell carcinoma.
  • Author(s): Kondoh A, Takano K, Kojima T, Ohkuni T, Kamekura R, Ogasawara N, Go M, Sawada N, Himi T
  • Journal Title: Acta-Otolaryngol in press
  • Peer Reviewed
• [Presentation] RSウイルス感染によるヒト鼻粘膜上皮細胞のシグナル応答 (2010)
  • Author(s): 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
  • Organizer: 第49回日本鼻科学会
  • Place of Presentation: 札幌
  • Year and Date: 20100826-20100828
• [Presentation] ヒト鼻粘膜上皮細胞を用いたホップ水抽出物のTSLP産生抑制効果 (2010)
  • Author(s): 渕本潤, 小島隆, 小林直之, 亀倉隆太, 郷充, 大國毅, 小笠原徳子, 正木智之, 伊藤一敏, 氷見徹夫, 澤田典均
  • Organizer: 第49回日本鼻科学会
  • Place of Presentation: 札幌
  • Year and Date: 20100826-20100828
• [Presentation] RSV感染鼻粘膜上皮細胞におけるIII型インターフェロンの重要性 (2010)
  • Author(s): 岡林環樹, 小島隆, 正木智之, 横田伸一, 堤裕幸, 氷見徹夫, 澤田典均, 藤井暢弘
  • Organizer: 2010日本インターフェロンサイトカイン学会
  • Place of Presentation: 福岡
  • Year and Date: 20100625-20100626
• [Presentation] RSウイルス感染ヒト鼻粘膜上皮細胞におけるタイト結合の誘導 (2010)
  • Author(s): 正木智之, 小島隆, 大國毅, 小笠原徳子, 氷見徹夫, 村田雅樹, 田中敏, 澤田典均
  • Organizer: 第99回日本病理学会
  • Place of Presentation: 東京
  • Year and Date: 20100427-20100429
• [Presentation] RSウイルス感染ヒト鼻粘膜上皮細胞におけるタイト結合の誘導 (2010)
  • Author(s): 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
  • Organizer: 第28回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 福井
  • Year and Date: 20100218-20100220
• [Presentation] 正常ヒト鼻粘膜上皮バリア調節機構へのTLRの関与 (2009)
  • Author(s): 大國毅, 小島隆, 小笠原徳子, 正木智之, 氷見徹夫, 澤田典均
  • Organizer: 第8回コネキシン研究会
  • Place of Presentation: 福岡
  • Year and Date: 20091126-20091128
• [Presentation] ウイルス感染とヒト鼻粘膜バリア (2009)
  • Author(s): 正木智之, 小島隆, 大國毅, 小笠原徳子, 澤田典均, 氷見徹夫
  • Organizer: 第48回日本鼻科学会
  • Place of Presentation: 島根
  • Year and Date: 20091001-20091003
• [Presentation] 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 (2009)
  • Author(s): 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
  • Organizer: 第98回日本病理学会
  • Place of Presentation: 京都
  • Year and Date: 20090501-20090503
• [Presentation] 核内受容体PPAR-gammaを介したヒト鼻粘膜上皮細胞および樹状細胞のタイト結合の発現調節機構 (2008)
  • Author(s): 小笠原徳子, 小島隆, 郷充, 亀倉隆太, 澤田典均, 氷見徹夫
  • Organizer: 日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 20081127-20081130
• [Presentation] ヒト鼻粘膜におけるタイト結合蛋白tricellulinの発現調節 (2008)
  • Author(s): 大國毅, 小島隆, 亀倉隆太, 小笠原徳子, 菊池真, 二宮孝文, 氷見徹夫, 澤田典均
  • Organizer: 第40回日本臨床分子形態学学会
  • Place of Presentation: 福岡
  • Year and Date: 20081003-20081004
• [Presentation] 核内受容体PPAR-gammaを介したヒト鼻粘膜上皮細胞および樹状細胞のタイト結合の発現調節機構 (2008)
  • Author(s): 小笠原徳子, 小島隆, 郷充, 亀倉隆太, 澤田典均, 氷見徹夫
  • Organizer: 第29回日本炎症再生学会
  • Place of Presentation: 東京
  • Year and Date: 20080708-20080710
• [Book] Gap and tight junctions in liver : composition, regulation, and function. The Liver : Biology and Pathobiology, 5th Edition(edited by Arias IM, et al.) (2009)
  • Author(s): Kojima T, Sawada N, Yamaguchi H, Fort AG, Spray DC.
  • Total Pages: 201-220
  • Publisher: Lippincott Williams&Wilkins, Philadelphia
• [Patent(Industrial Property Rights)] TSLP過剰発現抑制剤 (2009)
  • Inventor(s): 澤田典均、小島隆、淵本潤、小林直之
  • Industrial Property Rights Holder: 札幌医科大学、サッポロビール株式会社
  • Industrial Property Number: 特許,2009-2779276
  • Filing Date: 2009-12-07
  • Overseas