hBD gene transfection protect against bacterial infection in vivo

• Project/Area Number: 15592196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: KAKU Tohru Health Sciences University of Hokkaido, Dentistry, Professor, 歯学部, 教授 (60133253)
• Co-Investigator(Kenkyū-buntansha): ABIKO Yoshihiro Health Sciences University of Hokkaido, Dentistry, Professor, 歯学部, 教授 (90260819) ; NAKASHIMA Keisuke Health Sciences University of Hokkaido, Dentistry, Associate Professor, 歯学部, 助教授 (80227785) ; ARAKAWA Toshiya Health Sciences University of Hokkaido, Dentistry, Assistant Professor, 歯学部, 講師 (40306254)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: Defensin / Transfection / Bacterial infection / Periodontitis / Apoptosis / βディフェンシン / 抗細菌性蛋白 / 口腔扁平上皮癌 / 抗細菌性タンパク

Research Abstract

The human beta defensins (hBDs), a group of antimicrobial peptides, produced by oral epithelial cells contribute to a defensive mechanism for bacterial infection. The expression level of hBDs in KB cell derived from carcinoma is much lower than that in cells derived from normal oral epithelium. We have previously shown apoptotic cell death in KB cells induced by Actinobacillus actinomycetemcomitance (Aa) involved in progressive periodontal disease. Increased expression of hBD-2 by transfection of their genes inhibited the apoptotic cell death. The results suggest that increased expression of hBDs make them resistant bacterial infection. This data may provide a possibility of preventative gene therapy for periodontal disease. In vivo data is required for a proof the possibility. In the present study, we examined whether increased expression hBDs make them resistance Aa infection in vivo. The hBD genes were transfected with Adeno virus into tumor tissues formed by KB cells transplanted in nude mice. The infection rate was evaluated by size of tumor mass and number of abscess formation. Increased expression of hBDs in the tumors at both mRNA and protein levels. The infection rate in the gene transfection was a significantly lower than that in non-gene transfection. The results indicate that hBD gene transfection may be useful for prevention of bacterial infection.

Research Products

• [Journal Article] Impaired alveolization in mice deficient in membran-type matrix metalloproteinase 1(MT1-MMP) (2005)
  • Author(s): Irie K, Komori K, Seiki M, Tsuruga E, Sakakura Y, Kaku T, Yajima T
  • Journal Title: Med Mol Morphol 38(1) Pages: 43-46
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cell proliferation. apoptosis and apoptosis-related factors in odontogenic keratocysts and dentigerous cysts (2005)
  • Author(s): Kichi E, Emokiya Y, Muramatsu T, Hashimoto S, Inoue T, Abiko Y, Shimono M
  • Journal Title: J. Oral Pathol. Med. 34 Pages: 280-286
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Akiyama M, JRMcMillian, Abiko Y, Shimazu H
  • Journal Title: Virchow Arch. 12 Pages: 857-861
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A new paradiium of Titanium-bone bonding : Creation of the collaboration zone between the both substances, by use of 3-D titanium web, which is attached to the titanium bulk by vacuum sintering (2005)
  • Author(s): Kuboki Y, Yoshimoto R, Kakto H, Li D, Kaku T, Tanaka T, Kaneko M, Yanagisawa A, Tsuru K, Osaka A, Shiota H, Seki Y, Takita H.
  • Journal Title: Archives of Bioceramics Research 5(24) Pages: 146-149
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Single-nucleotide polymorphisin(SNP) in β-defensin 2 in a Japanese population and an effect of-1029 SNP on promoter activity (2005)
  • Author(s): Kusano K, Abiko Y, Nishimura M, Arakawa T, Takeshima M, Fujimoto A, Takuma T, Kaku T
  • Journal Title: Oral Science International 2(2) Pages: 80-84
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and dentigerous cysts (2005)
  • Author(s): Kichi E, Emokiya Y, Muramatsu T, Hashimoto S, Inoue T, Abiko Y, Shimono M
  • Journal Title: J.Oral Pathol.Med. 34 Pages: 280-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Akiyama M, JR McMillian, Abiko Y, Shimazu H
  • Journal Title: Virchow Arch. 12 Pages: 857-861
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Single-nucleotide polymorphism(SNP) in β-defensin 2 in a Japanese population and an effect of-1029 SNP on promoter activity (2005)
  • Author(s): Kusano K, Abiko Y, Nishimura M, Arakawa T, Takeshima M, Fujimoto A, Takuma T, Kaku T
  • Journal Title: Oral Science International 2(2) Pages: 80-84
  • NAID: 10020401549
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Impaired alveolarization in mice deficient in membarane-type matrix metalloproteinase (MT1-MMP) (2005)
  • Author(s): Irie K., Komori K., Seiki M., Sakakura U, Kaku T, Yajima T
  • Journal Title: Med Mol Morphol 38(1) Pages: 43-46
• [Journal Article] A new paradigm of taitanium-bone bonding=creation of the collaboration zone between the both substanaces, by use of 3-S titanium web, which is attatached to the titanium bulk by vacuum sintering (2005)
  • Author(s): Kuboki Y, Yoshimoto R, Katoh H, Li D, Kaku T, Tanaka T, Kaneko M, Yanagisawa A, Tsuru K, Osaka A, et al.
  • Journal Title: Archives of Bioceramics Reseach 5 Pages: 146-149
• [Journal Article] Single-nucleotide polymorphism(SNP) in beta-difensin 2 in a Japanese population and an effect of -1029 SNP on promoter activity (2005)
  • Author(s): Kusano K, Abiko Y, Nishimura M, Arakawa T, Takeshima M, Fujimoto A, Takuma T, Kaku T.
  • Journal Title: Oral Science International 2(2) Pages: 80-84
• [Journal Article] 成長期ラット顎関節円板におけるversican isoform mRNAの発現-TaqMan probeを用いたreal-time quantitative PCRによる分析- (2005)
  • Author(s): 鳥谷奈保子, 荒川俊哉, 田隈泰信, 安彦善裕, 溝口到
  • Journal Title: 北海道医療大学歯学会雑誌 24(1) Pages: 31-39
  • NAID: 110004622816
• [Journal Article] Beta defensin-s engineered epidermis shows highly protective effect fro bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Shibaki A, Akiyama M, McMillan JR, Abiko Y, Shimizu H.
  • Journal Title: Gene Therapy 12 Pages: 857-861
• [Journal Article] Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and in dentigerous cysts (2005)
  • Author(s): Kichii E, Enokiya Y, Muramatsu T, Hashimoto S, Inoue T, Abiko Y, Shimono M.
  • Journal Title: J Oral Pathol Med 36 Pages: 280-286
• [Journal Article] Current dental implant research (2005)
  • Author(s): Inoue T, Matsuzaka K, Yoshinari M, Tanaka T, Abiko Y., Shimono M.
  • Journal Title: Dentistry in Japan 41 Pages: 196-213
• [Journal Article] 口腔扁平苔癬におけるβディフェンシン2の発現と臨床病理学的所見との関連についての検討 (2004)
  • Author(s): 野口忠秀, 神部芳則, 草間幹夫, 安彦善裕, 賀来 亨
  • Journal Title: 目口粘膜誌 10(1) Pages: 6-10
  • NAID: 10013391951
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Correlated expression of human beta defensin-1,-2 and -3 mRNAs in gingival tissues of young children (2004)
  • Author(s): Saitoh M, Abiko Y, Shimabukuro S, Kusano K, Nishimura M, Arakawa T, Nakashima K, Takuma T, Kaku T, Igarashi S
  • Journal Title: Arch Oral Biol. 49 Pages: 799-803
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effecyt of defensin peotides on eukaryotic cells : primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura M, Abiko Y, Kurashige Y, Takeshima M, Yamazaki M, Kusano K, Saitoh M, Nakashima K, Inoue T, Kaku T
  • Journal Title: J. Dermatol Sci. 36(2) Pages: 87-95
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An immunohistochemical study of the localization of inducible nitric oxide bynthase(iNOS) and heat shock protein (HSP) in pleomorphic adenoma (2004)
  • Author(s): Yamaguchi M, Abiko Y, Nishimura M, Saitoh M, Kaku T
  • Journal Title: cta Histochem. Cytochem. 37(4) Pages: 267-271
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 小児歯肉におけるβディフェンシン-1,-2,-3mRNAの発現及び局在 (2004)
  • Author(s): 齊藤正人, 島袋鎮太郎, 坂口也子, 櫻井有子, 野呂大輔, 菅谷裕行, 五十嵐清治, 西村学子, 安彦善裕
  • Journal Title: 小児歯科学雑誌 42(1) Pages: 69-74
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effect of melatonin on prostaglandin E2-induced pro-inflammatory cytokine production in human gingival fibroblasts (2004)
  • Author(s): Fujii T, Wang P, Saito T, Kaku T, Usui S, Otogoto J, Ota N, Baehni PC
  • Journal Title: J.Hard Tissue Biology 13(1) Pages: 24-28
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Correlated expression of human beta defenshin-1, -2 and -3 mRNAs in Gingival tissue of young children (2004)
  • Author(s): Saito M, Shimabukuro S, Sakaguchi N, Sakurai Y, Noro D, Sugaya H, Igarashi S, Nishimura M, Abiko Y
  • Journal Title: Journal of Pediatric Dentistry 42(1) Pages: 69-74
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Upregulation of human beta-defensin 2 peptide expression in oral lichen planus, clinicopathological Study (2004)
  • Author(s): Noguchi T, Kanbe Y, Kusama M, Abiko Y, Kaku T
  • Journal Title: Journal of Oral Mucous Membrane 10(1) Pages: 6-10
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effect of defensin peotides on eukaryotic cells : primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura M, Abiko Y, Kurashige Y, Takeshima M, Yamazaki M, Kusano K, Saitoh M, Nakashima K, Inoue T, Kaku T
  • Journal Title: J.Dermatol Sci. 36(2) Pages: 87-95
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An immunohistochemical study of the localization of inducible nitric oxide synthase(iNOS) and heat shock protein (HSP) in pleomorphic adenoma (2004)
  • Author(s): Yamaguchi M, Abiko Y, Nishimura M, Saitoh M, Kaku T
  • Journal Title: Acta Histochem. Cytochem. 37(4) Pages: 267-271
  • NAID: 110003144388
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of melatonin on prostaglandin E2-induced pro-inflammatory cytokine production in human gingival fibroblasts (2004)
  • Author(s): Fujii T, Wang P-L, Saito T, Kaku T, Usuii S, Otogoto J, Ota N, Baehni P
  • Journal Title: Journal of Hard Tissue Biology 13(1) Pages: 24-28
• [Journal Article] シイナスリフトの隣在歯への影響について-術後5年経過症例- (2004)
  • Author(s): 小川 優, 清川宗克, 石井良明, 中林淳, 鈴木崇夫, 三上格, 新井田淳, 賀来亨
  • Journal Title: 日本口腔インプラント学会誌 17(1) Pages: 54-59
• [Journal Article] C-ternimal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells (2004)
  • Author(s): Okumura K, Itoh A, Isogai E, Hirose K, Hosokawa Y, Abiko Y, Shibata T.
  • Journal Title: Cancer Letters 212 Pages: 185-194
• [Journal Article] ウサギ頭頂骨に設置したキャップ内の骨形成に対するplatelet-rich plasma影響 (2004)
  • Author(s): 川田丈司, 廣瀬由紀人, 越智守生, 賀来亨, 矢嶋俊彦
  • Journal Title: 東日本歯学雑誌 23(1) Pages: 15-29
  • NAID: 120005454807
• [Journal Article] 口腔扁平苔癬におけるβディフェンシン2の発現と臨床病理学的所見との関連についての検討 (2004)
  • Author(s): 野口忠秀, 神部芳則, 草間幹夫, 安彦善裕, 賀来 亨
  • Journal Title: 日本口腔粘膜学会雑誌 10(1) Pages: 6-10
  • NAID: 10013391951
• [Journal Article] Correlated expression of human beta defensin-1,-2 and -3 mRNAs in gingival tissues of young children (2004)
  • Author(s): Saitoh M, Abiko Y, Shimabukuro S, Kusano K, Nishimura M, Arawaka T
  • Journal Title: Archives of Oral Biology 49 Pages: 799-803
• [Journal Article] Effect of defensin peptides on eukaryotic cells : primary epithelial cells, fibro blasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura M, Abiko Y, Kurashige Y, Takeshima M, Yamazaki N, Kusano
  • Journal Title: Journal of Dermatological Science 36 Pages: 87-95
  • NAID: 10016185292
• [Journal Article] An Immunohistochemical study of the localization inducible nitric oxide synthase(iNOS) and heat shock protein(HSP) in pleomorphic adenoma (2004)
  • Author(s): Yamaguchi M, Abiko Y, Nishimura M, Saitoh M, Kaku T
  • Journal Title: Acta Histochemica et Cytochemica 37(4) Pages: 267-271
  • NAID: 110003144388
• [Journal Article] アパトイト-プラストーインプラントの実験的研究 (2004)
  • Author(s): 松原秀樹, 廣瀬由紀人, 賀来 亨, 越智守生, 坂口邦彦
  • Journal Title: 東日本歯学雑誌 23(2) Pages: 197-209
• [Journal Article] Expression of MIP-3 α/CCL20, a macrophage inflammatoly protein in oral squamous cell carcinoma (2003)
  • Author(s): Abiko Y, Nishimura M, Kusano K, Nakashima K, Okumura K, Arakawa T, Takuma T, Mizoguchi I, Taku T
  • Journal Title: Archives of Oral Biology 48 Pages: 171-175
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ultrastructural study of synovitis induced by trauma to the rat temporomandibular joint(TMJ) (2003)
  • Author(s): Muto T, Shigeo K, Kanazawa M, Irie K, Yajima T, Kaku T
  • Journal Title: J Oral Pathol Med 32 Pages: 25-33
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Upregulated expression of human β defensin-1 and -3 mRNA differentiation of keratinocyte immortalized cell lines, HaCaT and PHK16-0b (2003)
  • Author(s): Abiko Y, Nishimura M, Kusano K, Yamazaki M, Arakawa T, Takuma T, Kaku T
  • Journal Title: Journal of Dermatol Science 31 Pages: 225-228
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Localization of human β-defensin 3 mRNA in normal oral epithelium, leukoplakia, and lichen planus : an in situ hybridization study (2003)
  • Author(s): NishimuraM, Abiko Y, Kusano K, Yamazaki M, Saitoh M, Mizoguchi I, Jinbu Y, Noguchi T, Kaku T
  • Journal Title: Med. Electron Microsc. 36(2) Pages: 94-97
  • NAID: 10011996435
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Defensins in saliva and the salivary glands (2003)
  • Author(s): Abiko Y, Nishimura M, Kaku T
  • Journal Title: Med. Electron Microsc. 36(4) Pages: 247-252
  • NAID: 80016427236
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of MIP-3 α/CCL20, a macrophage inflammatoly protein in oral squamous cell carcinoma (2003)
  • Author(s): Abiko Y, Nishimura M, Kusano K, Nakashima K, Okumura K, Arakawa T, Takuma T, Mizoguchi I, Kaku T
  • Journal Title: Archives of Oral Biology 48 Pages: 171-175
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Localization of human β-defensin 3 mRNA in normal oral epithelium, leukoplakia, and lichen planus : an in situ hybridization study (2003)
  • Author(s): Nishimura M, Abiko Y, Kusano K, Yamazaki M, Saitoh M, Mizoguchi I, Jinbu Y, Noguchi T, Kaku T
  • Journal Title: Med.Electron Microsc. 36(2) Pages: 94-97
  • NAID: 10011996435
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Defensins in saliva and the salivary glands (2003)
  • Author(s): Abiko Y, Nishimura M, Kaku T
  • Journal Title: Med.Electron Microsc. 36(4) Pages: 247-252
  • NAID: 80016427236
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biological characteristics of the junctional epithelium (2003)
  • Author(s): Shimono M, Ishikawa T, Enokiya Y, Muramatsu T, Matsuzaka K, Inoue T, Abiko Y, Yamaza T, Kido M A, Tanaka T, Hashimoto S
  • Journal Title: J.Electron Microsc. 52(6) Pages: 627-639
  • NAID: 10011951305
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] ティッシュエンジニアリング 2005 (2005)
  • Author(s): 監修 日本組織工学会, 田畑泰彦, 岡野光夫編
  • Total Pages: 238
  • Publisher: 日本医学館
• [Publications] Abiko Y, Nishimura M, Kusano K, Nakashima K, Okumura K, Arakawa T, Takuma T, Mizoguchi I, Kaku T.: "Expression of MIP-3α/CCL20, a macrophage inflammatory protein in oral squamous cell carcinoma"Archiv Oral Biol. 48. 171-175 (2003)
• [Publications] Abiko Y, Nishimura M, Kusano K, Yamazaki Y, Arakawa T, Takuma T, Kaku T.: "Upregulated expression of human β defensin-1 and -3 mRNA differentiatior of keratinocyte immortalized cell lines, HaCaT and PHK16-0b"J Dermatol Sci. 31. 225-228 (2003)
• [Publications] Nishimura M, Abiko Y, Kusano K, Yamazaki M, Saitoh M, Mizoguchi I, Jinbu Y, Noguchi T, Kaku T.: "Localization of human β-defensin 3 mRNA in normal oral epithelium, leukoplakia, and lichen planus : an in situ hybridization study"Med Electron Microsc. 36(1). 94-97 (2003)
• [Publications] Abiko Y, Nishimura M, Kaku T.: "Defensins in saliva and the salivary glands"Med Electron Microsc. 36(4). 247-252 (2003)
• [Publications] Abiko Y, Ogawa I, Hattori Y, Kusano K, Nishimura M, Ohuchi T, Abe U, Shibata T, Matsuda S, Takata T, Kaku T.: "Atypical carcinoid (neuroendocrine carcinoma) of the gingival : Counterpart of a laryngeal tumor"Pathology International. 54. 97-100 (2004)