| Project/Area Number |
18390498
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ARAKAKI Rieko The University of Tokushima, Graduate School of Institution of Health Bioscience, Assistant Professor (40231120)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIMARU Naozumi The University of Tokushima, Graduate School of Institution of Health Biosdence, Associate Professor (60314879)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,130,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2007: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2006: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | autoimmune disease / sex difference / estrogen deficiency / apontosis / autoantigen / salivary eland / Interferon-gamma / シェーグレン症候群 |
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| Research Abstract |
Although a number of autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. We have recently reported that estrogen deficiency induces apoptotic cells in the salivary and lacrimal glands from ovariectomized (Ovx) C57BL/6 (B6) mice (Mol. Cell. Biol. 26: 2949, 2006). It has been well documented that the aberrant major histocompatibility complex (MHC) class II molecules may contribute to the development of autoimmunity, the precise mechanisms of MHC class II expression in the epithelial cells in the target tissues of autoimmune diseases remains obscure. In this study, we have investigated the molecular mechanisms responsible for tissue-specific MHC class II expression caused by estrogen deficiency. The regulation of MHC class II expression is under the control of a complex cytokine network that requires the coordinated action of multiple transcription factors and co-activators. Among them, Class II transactivator (CIITA) is a key regulator of MHC class H expression. Prominent MHC class II expression was observed in salivary gland from Ovx B6 mice, not in those from Sham-B6 mice. Estrogen deficiency also induced interleukin-18 (IL-18) which known as interferon (IFN)-gamma-inducing factor, IFN-gamma, interferon regulatory factor-1 (IRF-1) and CIITA expression in salivary and lacrimal glands of Ovx B6 mice. In vitro, tamoxifen, antiestrogenic agent, induced IL-18, IRF-1, CIITA and MHC class II expression in cultured salivary gland cell. These results suggest that estrogen deficiency induces both apoptosis and CIITA-induced MHC class II expression through IFN-gamma dependent mechanism in the epithelial cells in the target organ of autoimmune diseases. Estrogen deficiency dependent MHC class II expression in the exocrine gland cells may play a possible role for gender-based autoimmunity in postmenopausal women.
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