2005 Fiscal Year Final Research Report Summary
Development of drug treatment for endometriosis targeting cytokine signal transduction molecules
| Project/Area Number |
16591659
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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 |
Obstetrics and gynecology
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| Research Institution | National University Corporation Tottori University |
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Principal Investigator |
HARADA Tasuku Tottori University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (40218649)
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| Co-Investigator(Kenkyū-buntansha) |
TERAKAWA Naoki Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (90163906)
IWABE Tomio Tottori University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (10284001)
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| Project Period (FY) |
2004 – 2005
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| Keywords | endometriosis / interleukin-8 / interleukin-6 / tumor necrosis factor alpha / NF-kB / progesterone / danazol / dienogest |
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| Research Abstract |
We previously showed that interleukin-8(IL-8) and tumor necrosis factor-a(TNFa) are significantly elevated in the PF of women with endometriosis compared with that of women without endometriosis and that peritoneal fluid levels of IL-8 significantly enhanced proliferation of stromal cells derived from ovarian endometriomas. We further determined that gene and protein expression of IL-8 in the stromal cells of endometriotic tissues are up-regulated by TNFa and that TNFa stimulates the proliferation of endometriotic stromal cells (ESCs). This stimulatory effect of TNFa was mediated by IL-8. In addition, we demonstrated that adding TNFa stimulated IL-8 gene and protein in ESCs. Activation of the transcription factor, nuclear factor-kB (NF-kB), has been shown to play an important role in the enhanced expression of several cytokine genes, including IL-6 and IL-8. Activation of NF-kB is shown to be critical for TNFa-induced IL-8 expression in ESCs. We undertook the present study to determine the effect of anti-NF-kB drugs, antisence for cytokine RNA and sex steroid hormones (progesterone, dienogest and danazol) on IL-8 production induced by TNFa in ESCs. The results of present study demonstrates that P4, danazol and dienogest attenuate the TNFa induced IL-8 gene and protein expression via inhibiting NF-kB activation in ESCs. Our series of experiments strongly suggest that these hormonal agents may inhibit progression of endometriosis through reducing the expression of growth promoting cytokines. The results may implicate a possible molecular mechanism of hormone therapy for alleviating endometriosis.
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