Tunicamycin enhances the apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand in endometriotic stromal cells

Author： Hasegawa Akiko Osuga Yutaka Hirota Yasushi Hamasaki Kahori Kodama Ako Harada Miyuki Tajima Toshiki Takemura Yuri Hirata Tetsuya Yoshino Osamu Koga Kaori Yano Tetsu Taketani Yuji

Publisher： Oxford University Press

ISSN： 1460-2350

Source： Human Reproduction, Vol.24, Iss.2, 2009-02, pp. : 408-414

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Abstract

BACKGROUND The increase in concentration of osteoprotegerin, an antagonist of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the peritoneal fluid of women with endometriosis may interfere with TRAIL-induced apoptosis in endometriotic cells and promote the development of endometriosis. In the present study, the effect of tunicamycin, a possible apoptosis enhancer, on TRAIL-induced apoptosis in endometriotic stromal cells (ESC) was determined. METHODS ESC were isolated from cyst walls of ovarian endometrioma and cultured. ESC were incubated with or without tunicamycin (2 g/ml) for the first 16 h, and then incubated with or without TRAIL (200 ng/ml) for the following 24 h. To examine whether caspases were involved in TRAIL-induced apoptosis, z-VAD-fmk (30 M), a general caspase inhibitor, was added 1 h before TRAIL treatment. ESC were transfected with small interfering RNA (siRNA) for DR5, a receptor of TRAIL, before tunicamycin treatment to evaluate its role in ESC. DR5 mRNA level was determined by quantitative RTPCR. Apoptosis in ESC was evaluated by flow cytometry. RESULTS Tunicamycin increases both DR5 mRNA (P < 0.005)="" and="" trail-induced="" apoptosis="">P < 0.0001)="" in="" esc.="" the="" increase="" in="" trail-induced="" apoptosis="" in="" esc="" by="" tunicamycin="" was="" suppressed="">P < 0.05)="" by="" z-vad-fmk.="" transfection="" with="" dr5="" sirna="" suppressed="" the="" tunicamycin-induced="" increase="" in="" dr5="" mrna="" and="" abrogated="" the="" up-regulation="" of="" trail-induced="" apoptosis="" by=""> CONCLUSIONS The combined treatment with tunicamycin and TRAIL may have therapeutic potential in the treatment of endometriosis.