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2003 Fiscal Year Final Research Report Summary

Inflammation by mast cell kininogen and its suppression -Development of a new drug

Research Project

Project/Area Number 13557154
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

HOSOI Kazuo  The University of Tokushima, School of Dentistry, Professor, 歯学部, 教授 (10049413)

Co-Investigator(Kenkyū-buntansha) AKAMATSU Tetsuya  The University of Tokushima, School of Dentistry, Professor, 歯学部, 助手 (80294700)
HANEJI Tatsuji  The University of Tokushima, School of Dentistry, Professor, 歯学部, 教授 (50156379)
NAKAJO Nobuyoshi  The University of Tokushima, School of Dentistry, Professor, 歯学部, 教授 (80069046)
Project Period (FY) 2001 – 2003
KeywordsKininogen / Acute phase protein / Inflammation cytokine / LPS / exocrine gland / Salivary gland
Research Abstract

We have focussed on the mast cells appearing in salivary gland, oral mucosa, and other tissues, and examined the bioactive substances present in these cells. We found that the mast cells present in these tissues and peritoneal cavity expressed high molecular weight-kininogen and T-I kininogen and these protein products were stored in the secretory granules in these cells (2000-2001). On the other hand, the salivary gland cells other than mast cells did not show the kininogen expression, although there are reports indicating that these inflammation proteins are expressed in the salivary gland parenchymal cells
On the other hand, the salivary gland produces the various cytokins other than these inflammation proteins. We therefore examined how the expression of these cytokines are regulated by the inflammation signals prompted in the oral cavity or in the whole body. We also tried to find out the function of the salivary gland in the defense system in the oral cavity. Using C3H/HeJ and C3H … More /HeN mice (mutant strain defective of Toll-like receptor and its wild type strain), we examined how inflammation cytokines were induced by systemic injection of LPS. In vivo experiments, injection of LPS induced the expression of n-1β strongly and TNF-α and IL-6 weakly (2002)
We next showed that IL-lei was localized in the secretory granules of the granular convoluted tubular cells. We also found that the size of salivary gland IL-1β is 17 kDa although the mRNA corresponding to 35 kDa IL-1β precursor was synthesized in the submandibular gland. It is therefore conceivable that 35 kDa IL-1β precursor was hydrolyzed to the 17 kDa secretory form in the salivary gland. Since kallikrein mK1, mK9, mK13, and mK22 are localized in the secretory granules of the submandibular gland, we incubated 35 kDa IL-1β with these kallikreins. The result showed that mK13 is an enzyme which gave 17 kDa IL-1β. We are now investigating the cleavage site in 35 kDa IL-1β by mK13
Strict defense system would be required for oral cavity since the oral cavity is a major barrier of harmful foreign antigens or bacteria in the body. The present study implies the existence of "Oral cavity Salivary gland axis" as a defense system, by which inflammation occurred in the oral cavity may be healed by interaction with the salivary gland Less

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Wei, W.et al.: "Induction of C-reactive protein, serum amyloid P component, and kininogens in the submandibular and lacrimal glands of rats with experimentally induced inflammation"Life Sciences. 69(3). 359-368 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurabuchi, S. et al.: "Androgen regulation of the cellular distribution of the true tissue kallikrein mK1 in the submandibular gland of the mouse"Journal of Histochemistry and Cytochemistry. 49(6). 801-802 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Parvin, M.N. et al.: "Expression localization of AQP4 in the crypt epithelial cells of the rat duodenum"Biomedical Research. 12(2). 77-82 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Parvin, M.N.: "Structure, function, and transcriptional regulation of aquaporins, proteins of the water channel family"Dentistry in Japan. 37. 26-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 倉淵真悟 他: "マウス顎下腺顆粒性導管の性差とホルモンによる調節-免疫組織化学的解析-"日本咀嚼学会雑誌. 10(2). 61-70 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Parvin, M.N., et al.: "Expression and hormone-induced redistribution of AQP5 in Brunner's gland of the rat duodenum"Biochimica et Biophysica Acta : Molecular Cell Research. 1542(1-3). 116-124 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurabuchi, S. et al.: "Developmental and androgenic regulation of the immunocytochemical distribution of mK1, a true tissue kallikrein, in the granular convoluted tubule of the mouse submandibular gland"Journal of Histochemistry and Cytochemistry. 50(2). 135-145 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanamori, N. et al.: "Methylene blue as a vascular filling dye"ITE LETTERS on Batteries, New Technologies & Medicine (with News). 3(1). 75-77 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurabuchi, S. et al.: "Multihormonal regulation of granular convoluted tubular cells expressing mK1, a true tissue kallikrein, in the mouse submandibular gland"Proceedings of the 21st Conference of European Comparative Endocrinologists. 527-530 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murdiastuti, K. et al.: "Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats"Pfl gers Archives- European Journal of Physiology. 445(3). 405-412 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akamatsu, T. et al.: "Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland"Pfl gers Archives- European Journal of Physiology. 446(6). 641-665 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yano, Y. et al.: "Immunohistochemical distributions of the tissue kallikrein-kinin system in ischemic and non-ischemic mouse heart"Journal of Cadiovascular Pharmacology. 42(Suppl.1). S49-S53 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Foga a, S.E. et al.: "Difference in substrate and inhibitor sequence specificity of human, mouse and rat tissue kallikreins"Biochemical Journal. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yao, C.et al.: "A cute phase protein induction by experimental inflammation in the salivary gland"Proceeding of 1st International Congress of Mastification and Heal. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 細井和雄(分担執筆)他: "分子細胞生物学基礎実験法 改訂第2版"南江堂. 654 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hosoi, K., et al., (Barret, A.J., Rowlings, N.D., Woessner, J.F.eds.): "Handbook of proteolytic enzymes, 2nd edition"Elsevier. 2368 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wei, W., M.N.Parvin, K.Tsumura, T.Akamatsu, J.Tada, N.Kanamori, K.Hosoi: "Induction of C-reactive protein, serum amyloid P component, and kininogens in the submandibular and lacrimal glands of rats with experimentally induced inflammation"Life Sciences. 69(3). 359-368 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurabuchi, S.K.Hosoi, E.W.Gresik: "Androgen regulation of the cellular distribution of the true tissue kallikrein mK1 in the submandibular gland of the mouse"Journal of Histochemistry and Cytochemistry. 49(6). 801-802 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parvin, M.N., K.Murdiastuti, T.Akamatsu, N.Kanamori, N.Maeda, K.Hosoi: "Expression and localization of AQP4 in the crypt epithelial cells of the rat duodenum"Biomedical Research. 12(2). 77-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parvin, M.N., J.Tada, T.Akamatsu, K.Hosoi: "Structure, function, and transcriptional regulation of aquaporins, proteins of the water channel family"Dentistry in Japan. 37. 26-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurabuchi, S.and Hosoi, K.: "Sexual dimorphism and hormonal regulation of granular convoluted tubule (GCT) cells of mouse submandibular gland -Immunohistochemical analysis-"Journal of Japanese Society for Mastication Science and Health Promotion. 10(2). 61-70 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Parvin, M.N., K.Tsumura, T.Akamatsu, N.Kanamori, K.Hosoi: "Expression and localization of AQP5 in the stomach and duodenum of the rat"Biochimica et Biophysica Acta Molecular Cell Research. 1542(1-3). 116-124 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurabuchi, S., K.Hosoi, E.W.Gresik: "Developmental and androgenic regulation of the immunocytochemical distribution of mK1, a true tissue kallikrein, in the granular convoluted tubule of the mouse submandibular gland"Journal of Histochemistry and Cytochemistry. 50(2). 135-145 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanamori, N., T.Akamatsu, C.Kosugi-Tanaka, M.N.Parvin, K.Hosoi: "Methylene blue as a vascular filling dye"ITE LETTERS on Batteries, New Technologies & Medicine (with News). 3(1). 75-77 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurabuchi, S., K.Hosoi, E.W.Gresik: "Multihormonal regulation of granular convoluted tubular cells expressing mK1, a true tissue kallikrein, in the mouse submandibular gland"Proceedings of the 21^<st> Conference of European Comparative Endocrinologists (edited by Rainer Keller, Heinrich Dircksen, Dieter Sedlmeier, Hubert Vaudry). 527-530 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murdiastuti, K., O.Miki, C.Yao, M.N.Parvin, C.Kosugi-Tanaka, T.Akamatsu, N.Kanamori, K.Hosoi: "Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats"Pflugers Archives-European Journal of Physiology. 445(3). 405-412 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akamatsu, T., M.N.Parvin, K.Murdiastuti, C.Kosugi-Tanaka, C.Yao, O.Miki, N.Kanamori, K.Hosoi: "Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland"Pflugers Archives-European Journal of Physiology. 446(6). 641-651 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yano, Y., R.Ozono, H.Nakashima, Y.Oishi, M.Kambe, K.Hosoi, T.Oshima: "Immunohistochemicai distributions of the tissue kallikrein-kinin system in jschemic and non-ischemic mouse heart"Journal of Cadiovascular Pharmacology. 42(Suppl.1). S49-S53 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fogaca, S.E., R.L.Melo, D.C.Pimenta, K.Hosoi, L.Juliano, M.A.Juliano: "Difference in substrate and inhibitor sequence specificity of human, mouse and rat tissue kallikreins"Biochemical Journal. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yao, C., W.Wei, K.Hosoi: "Acute phase protein induction by experimental inflammation in the salivary gland, (Proceedings for The 1st International Congress on Mastication and Health -Oral Health for Healthy Life September 15-18, 2002, Yokohama, Japan)"Journal of Japanese Society for Mastication Science and Health Promotion. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakuno, T., K.Nishikawa, K.Hosoi, T.Higuti, Arakaki Y.Horiuchi, Y.Matuo, K.Miyazaki (eds.): "Techniques in protein experiment, solubilization of membrane protein, immunoprecipitation, In situ hybridization, quantitative PCR, in Experimental Manual for Molecular Cell Biology (in Japanese) (compiled under the supervision of T.Horio)"Nankodo (Tokyo). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hosoi, K.: "Mouse kallikreins mK13 and mK26, in "Handbook of proteolytic enzymes, 2nd edition" (Edited by Barren A.J., Rawlings N.D., Woessner, Jr., J.F.)"Elsevier Science. (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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