2003 Fiscal Year Final Research Report Summary
Role of matrix met alloprot einases and cytokines in the development of endometriosis
| Project/Area Number |
14370534
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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 |
Obstetrics and gynecology
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| Research Institution | Tottori University School of Medicine |
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Principal Investigator |
TERAKAWA Naoki Tottori Univ., Dept.Obst et.Gynecol., Professor, 医学部, 教授 (90163906)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Fuminori Tottori Univ., Dept.Obst et.Gynecol., Research Associates, 医学部附属病院, 助手 (40322218)
IWABE Tomio Tottori Univ., Dept.Obst et.Gynecol., Assistant Professor, 医学部附属病院, 講師 (10284001)
HARADA Tasuku Tottori Univ., Dept.Obst et.Gynecol., Assistant Professor, 医学部, 講師 (40218649)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Endometriosis / Development and progression / Endometriotic stromal cells / Cytokine TNFα / IL-8 / Nuclear fact or-κB / Estrogen / GnRH agonist |
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| Research Abstract |
It is believed that the extracellular matrix (ECM) remodeling is relevant to the development and the progression of endometriosis. Tissue remodeling involving ECM turnover is regulated by the combined action of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). It has been reported that the concentration of MMP-1 is increased and that of TIMP-1 is decreased in peritoneal fluid of patients with endometriosis. The present study was undertaken to investigate the possible role of MMPs and TIMPs in the development of endometriosis. In this study, however, we did not find any difference in the levels of MMP-1 and TIMP-1 in peritoneal fluid between infertile patients with and without endometriosis.
We previously reported that TNF a promoted proliferation of endometriotic stromal cells by inducing IL-8 gene and protein expression. We hypothesize that TNF a may induce IL-S production in endometriotic cells through nuclear factor-κB (NF-κB) activation. Western blot analyses and EMSA revealed that incubation with TNF α induced the expression of p-I κB and activation of NF-κB in endometriotic stromal cells. The addition of TNF α (0.1ng/ml) significantly increased protein and gene expression of IL-8 in the cells of patients without GnRH agonist treatment, but this expression was not observed in the cells of patients with GnRHa. The addition of E2 (10^<-7>M) enhanced the expression of IL-8. However, in the cells of patients who received GnRHa treatment, TNF α and E2 did not show any significant effect. These findings demonstrate that NF-κ B activation is critical for TNF α-induced IL-8 expression in endometriotic stromal cells. The current study showed for the first time that GnRHa treatment attenuated the expression of IL-8 by reducing TNF α-induced NF-κB activation.
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Research Products
(16 results)
