Tumor necrosis factor-α induced the release of interleukin-6 from endometriotic stromal cells by the nuclear factor-κB and mitogen-activated protein kinase pathways

Nobuhiro Yamauchi, Yamauchi N, Harada T, Tasuku Harada, Fuminori Taniguchi, Taniguchi F, Yoshida S, Souichi Yoshida, Tomio Iwabe, Iwabe T, Naoki Terakawa, Terakawa N
Fertility and sterility · 2004 · vol. 82 , pp. 1023–1028 · doi:10.1016/j.fertnstert.2004.02.134 · PMID:15474068 · W2042067351
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Tumor necrosis factor-α stimulated interleukin-6 release from endometriotic stromal cells via activation of nuclear factor-κB and mitogen-activated protein kinase signaling pathways.

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Abstract

ObjectiveTo 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).DesignProspective study.SettingDepartment 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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Condition tags

endometriosis

MeSH descriptors

Endometriosis Interleukin-6 Mitogen-Activated Protein Kinases NF-kappa B Stromal Cells Tumor Necrosis Factor-alpha Blotting, Western Butadienes Butadienes Electrophoresis Endometriosis Endometriosis Enzyme Inhibitors Enzyme Inhibitors Enzyme-Linked Immunosorbent Assay Female Humans I-kappa B Proteins I-kappa B Proteins Interleukin-6

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