Roles of sex hormones in the pathogenesis of psoriasis vulgaris and their therapeutic efficacy
| Project/Area Number |
14570825
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Teikyo University |
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Principal Investigator |
KANDA Naoko Teikyo University, School of Medicine, Associate professor, 医学部, 助教授 (50260493)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Shinichi , 医学部, 教授 (90114719)
ONISHI Takamitsu , 医学部, 講師 (80233211)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | psoriasis vulgaris / 17β-estradiol / MCP-1 / RANTES / IP-10 / apoptosis / keratinocyte / Bcl-2 / 17β-エストラジオール / 表皮角化細胞 / エストロゲンレセプターβ / AP-1 / Sp1 / 転写 / ケモカイン / エストロゲンレセプター / NF-κB / cAMP / IFN-γ / STAT1α |
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| Research Abstract |
The aim of this project is to investigate the effects of sex hormones on
1.proliferation, DNA synthesis, or apoptosis in keratinocytes
2.autocrine growth factor production in keratinocytes
3.the production of pro- or anti-inflammatory cytokines, chemokines, or angiogenic factors in keratinocytes
4.the expression of cell-adhesion molecules or receptors for inflammatory cytokines or growth factors in keratinocytes
5.the expression of cytokeratins in keratinocytes.
Our results on project 1:
17β-estradiol (E2) binds GPR30 on the surface of keratinocytes and induces cAMP signal which enhances the expression of anti-apoptotic protein, Bcl-2 and thus suppresses apoptosis induced by oxidative stress.
Our results on project 4 :
(1)E2 suppresses Jak1,2/Stat1 signaling pathway via inducing cAMP signal in keratinocytes and thus suppresses the expression of IP-10, type 1 T cell-attracting chemokine.
(2)E2 suppresses transcriptional activities of Sp1 and AP-1 in keratinocytes and thus suppresses the expression of MCP-1, monocyte/macrophage-attracting chemokine.
(3)E2 suppresses transcriptional activity of NF-κB in keratinocytes and thus suppresses the expression of RANTES, type 1 T cell- and monocyte/macrophage-attracting chemokine.
These results suggest that E2 may suppress abnormally enhanced apoptosis of keratinocytes in psoriatic lesions and maintain skin homeostasis and that E2 may suppress the infiltration of type 1 T cells or monocyte/macrophages into psoriatic skin lesions and thus attenuate inflammation. These results indicate therapeutic efficacy of E2 for psoriasis. Projects 2,3,5 are now on-going.
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Report
(5 results)
Research Products
(20 results)
