The Cellular Inhibitor of Apoptosis Protein‐2 is a Possible Target of Novel Treatment for Endometriosis

Fuminori Taniguchi, Hiroko Higaki, Masao Izawa, Yukihiro Azuma, Eriko Hirakawa, Imari Deura, Tomio Iwabe, Kohkichi Hata, Tasuku Harada
American journal of reproductive immunology (New York, N.Y. : 1989) · 2014 · vol. 71(3) , pp. 278–285 · doi:10.1111/aji.12193 · PMID:24382102 · W1995866593
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Endometriotic stromal cells exhibit elevated cIAP-2 expression regulated by TNFα/NF-κB, and inhibiting IAPs reduces ESC viability and IL-8, suggesting cIAP-2 as a therapeutic target.

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Abstract

PROBLEM: How is the tumor necrosis factor (TNF) α-induced inhibitor of apoptosis (IAP) protein expression in endometriotic stromal cells (ESCs) involved in cell viability and signaling pathways? METHOD OF STUDY: Endometriotic stromal cells were isolated from ovarian chocolate cysts in 20 patients who underwent laparoscopic surgery. IAP protein expression and IκB phosphorylation were evaluated by Western blot analysis. Interleukin (IL)-8 protein expression and cell proliferation were assessed by ELISA. RESULTS: Cellular IAP (cIAP)-2 protein expression in endometriotic tissue was higher than that of endometrium. TNFα markedly enhanced cIAP-2 protein expression in ESCs. Pretreatment with a nuclear factor (NF)-κB inhibitor attenuated TNFα-induced cIAP-2 expression. An antagonist of IAPs abrogated TNFα-induced cIAP-2 protein expression and showed a decrease in TNFα-induced IL-8 protein expression and BrdU incorporation in ESCs. CONCLUSIONS: TNFα and its downstream NFκB pathway have proven to be critical regulators of highly expressed cIAP-2 in ESCs. cIAP-2 may be a novel therapeutic target for endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Inhibitor of Apoptosis Proteins Stromal Cells Cell Proliferation Cell Proliferation Cells, Cultured Endometriosis Endometriosis Endometrium Female Gene Expression Regulation Gene Expression Regulation Humans I-kappa B Proteins I-kappa B Proteins Inhibitor of Apoptosis Proteins Inhibitor of Apoptosis Proteins Inhibitor of Apoptosis Proteins Interleukin-8

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