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  • Title: Tumor necrosis factor-alpha induced the release of interleukin-6 from endometriotic stromal cells by the nuclear factor-kappaB and mitogen-activated protein kinase pathways.
    Author: Yamauchi N, Harada T, Taniguchi F, Yoshida S, Iwabe T, Terakawa N.
    Journal: Fertil Steril; 2004 Oct; 82 Suppl 3():1023-8. PubMed ID: 15474068.
    Abstract:
    OBJECTIVE: To examine the involvement of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) in the induction of interleukin-6 (IL-6) by tumor necrosis factor-alpha (TNF-alpha) in endometriotic stromal cells (ESC). DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. PATIENT(S): Twelve patients who underwent laparoscopic surgery. INTERVENTION(S): Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary. MAIN OUTCOME MEASURE(S): We determined the effect of TNF-alpha on the production of IL-6 and the effect of inhibitors for NF-kappaB and the MAPK pathway on IL-6 production using ELISA. Western blottings and electrophoretic mobility shift assays were used to detect activation of NF-kappaB and extracellular signal-regulated kinase 1/2 (ERK1/2). RESULT(S): The addition of TNF-alpha (0.1 ng/mL) significantly increased IL-6 protein in endometriotic stromal cells. Western blottings and electrophoretic mobility shift assays revealed that incubation with TNF-alpha induced degradation of inhibitor kappaB (I kappaB) and expression of phosphorylated ERK1/2. The NF-kappaB inhibitor (TPCK) and MAPK inhibitor (U0126) blocked the TNF-alpha-induced IL-6 expression. Electrophoretic mobility shift assay revealed that U0126 attenuated activator protein-1 (AP-1) activation induced by TNF-alpha. CONCLUSION(S): These findings demonstrate that NF-kappaB and AP-1 activation is critical for TNF-alpha-induced IL-6 expression in endometriotic stromal cells. Novel therapeutic modalities targeting these molecules may be possible in the near future.
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