To examine the involvement of nuclear factor κ B(NF κ B) and mitogen activated protein kinase (MAPK) in the induction of interleukin 6 (IL- 6) by tumor necrosis factor- α (TNF- α )in endometriotic stromal cells (E...To examine the involvement of nuclear factor κ B(NF κ B) and mitogen activated protein kinase (MAPK) in the induction of interleukin 6 (IL- 6) by tumor necrosis factor- α (TNF- α )in endometriotic stromal cells (ESC). Prospective study. Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. Twelve patients who underwent laparoscopic surgery. Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary. We determined the effect of TNF- α .on the production of IL- 6 and the effect of inhibitors for NF κ B and the MAPK pathway on IL- 6 production using ELISA. Western blottings and electrophoretic mobility shift assays were used to detect activation of NF κ B and extracellular signal regulated kinase 1/2 (ERK1/2). The addition of TNF- α (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- α in duced degradation of inhibitor κ B(I κ B) and expression of phosphorylated ERK1/2. The NF κ B inhibitor (TPCK) and MAPK inhibitor (U0126) blocked the TNF- α induced IL- 6 expression. Electrophoretic mobility shift assay revealed that U0126 attenuated activator protein- 1 (AP- 1) activation induced by TNF- α . These findings demonstrate that NF κ Band AP1 activation is critical for TNF- α induced IL- 6 expression in endometriotic stromal cells. Novel therapeutic modalities targeting these molecules may be possible in the near future.展开更多
文摘To examine the involvement of nuclear factor κ B(NF κ B) and mitogen activated protein kinase (MAPK) in the induction of interleukin 6 (IL- 6) by tumor necrosis factor- α (TNF- α )in endometriotic stromal cells (ESC). Prospective study. Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. Twelve patients who underwent laparoscopic surgery. Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary. We determined the effect of TNF- α .on the production of IL- 6 and the effect of inhibitors for NF κ B and the MAPK pathway on IL- 6 production using ELISA. Western blottings and electrophoretic mobility shift assays were used to detect activation of NF κ B and extracellular signal regulated kinase 1/2 (ERK1/2). The addition of TNF- α (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- α in duced degradation of inhibitor κ B(I κ B) and expression of phosphorylated ERK1/2. The NF κ B inhibitor (TPCK) and MAPK inhibitor (U0126) blocked the TNF- α induced IL- 6 expression. Electrophoretic mobility shift assay revealed that U0126 attenuated activator protein- 1 (AP- 1) activation induced by TNF- α . These findings demonstrate that NF κ Band AP1 activation is critical for TNF- α induced IL- 6 expression in endometriotic stromal cells. Novel therapeutic modalities targeting these molecules may be possible in the near future.
