2003 Fiscal Year Final Research Report Summary
Identification of animal model for autoimmune disease using conditional expression of transgene
| Project/Area Number |
14370584
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tsurumi University |
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Principal Investigator |
SAITO Ichiro Tsurumi University, School of Dental Medicine, Professor, 歯学部, 教授 (60147634)
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| Co-Investigator(Kenkyū-buntansha) |
KIDA Satoshi Tokyo University of Agriculture, Faculty of Applied Bioscience, Department of Bioscience, Associate Professor, バイオサイエンス学部, 助教授 (80301547)
TSUBOTA Kazuo Keio University, School of Medicine, Department of Ophthalmology, Professor, 医学部, 教授 (40163878)
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| Project Period (FY) |
2002 – 2003
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| Keywords | conditional expression / autoimmune disease / immunotolerance / Sjogren's syndrome / animal model |
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| Research Abstract |
Organ-specific autoimmune diseases are characterized by tissue destruction and functional decline due to autoreactive T cells that escape self-tolerance. Sjogren's syndrome (SS) is an autoimmune disorder affecting the salivary and lacrimal glands and leads to clinical symptoms of dryness of the mouth and eyes. It is important to make clear the molecular mechanism of secretion to examine salivary and lacrimal hypofunction in SS. It has been reported that the transcription CREB (cAMP response element-binding protein) regulates secretion in the salivary glands, but this is not clear. In this report, we explored in detail the role of CREB in murine parotid acinar cells. The results showed that carbachol (muscarinic acetylcholin agonist) and isoproterenol (β2-adrenergic agonist) markedly stimulated the phosphorylation of CREB in parotid acinar cells. The phosphorylation of CREB was decreased by atropine (muscarinic acetylcholin antagonist) and propranolol (β2-adrenergic antagonist).Furthermore, the phosphorylation was inhibited by the PKA inhibitor but not by the PLC inhibitor. In parotid acinar cells, amylase secretion was induced by carbachol and isoproterenol, and this secretion was decreased by the PKA inhibitor. These results indicated that the transcription CREB regulated secretion in parotid acinar cells, and salivary hypofunction was caused by the dominant-negative CREB. Therefore, to define the role of CREB in the exocrine glands, we generated transgenic mice using an inducible system to temporally repress CREB function, and induced expression of the dominant-negative CREB by tamoxifen in the salivary glands. The transgenic control system is useful not only to investigate the pathological mechanism of SS but also to study the cause of other diseases.
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Research Products
(14 results)
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[Publications] Saegusa, K., Ishimaru, N., Yanagi, K., Mishima, K., Arakaki, R., Suda, T., Saito, I., Hayashi, Y.: "Prevention and induction of autoimmune exocrinopathy is dependent on pathogenic autoantigen cleavage in murine Sjogren's syndrome"J.Immunol.. 169. 1050-1057 (2002)
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[Publications] Saegusa, K., Ishimaru, N., Yanagi, K., Arakaki, R., Ogawa, K., Saito, I., Katunuma, N., Hayashi, Y.: "Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity"J.Clin.Invest.. 110. 361-369 (2002)
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[Publications] Matsuoka, T., Okamoto, Y., Matsuzaki, Z., Endo, S., Ito, E., Tsutsumi, H., Williamson, R.A., Sakurai, H., Burton, D.R., Saito, I.: "Characteristics of immuinity induced by viral antigen or conferred by antibody via different administration routes"Clin.ExImmunol.. 130. 386-392 (2002)
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[Publications] Arakaki, R., Ishimaru, N., Saito, I., Kobayashi, M., Yasui, N., Sumida, T., Hayashi, Y.: "Development of autoimmune exocrinopathy resembling Sjogrens syndrome in adoptively transferred mice with autoreactive CD4 + T cells"Arthritis Rheum.. 48. 3603-3609 (2003)
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[Publications] Nagata, Y., Inoue, H., Yamada, K., Higashiyama, H., Mishima, K., Kizu, Y., Takeda, I., Mizuno, F., Hayashi, Y., Saito, I.: "Activation of Epstein-Barr Virus by saliva from Sjogrens syndrome patients"Immunol.. 111. 223-229 (2004)
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