Progesterone and progestational compounds attenuate tumor necrosis factor alpha–induced interleukin-8 production via nuclear factor kappaB inactivation in endometriotic stromal cells

Sayako Horie, Horie S, Tasuku Harada, Harada T, Masahiro Mitsunari, Mitsunari M, Fuminori Taniguchi, Taniguchi F, Tomio Iwabe, Iwabe T, Terakawa N, Naoki Terakawa
Fertility and sterility · 2005 · vol. 83(5) , pp. 1530–1535 · doi:10.1016/j.fertnstert.2004.11.042 · PMID:15866594 · W2035455398
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Progesterone and progestational compounds were found to reduce TNFα-induced IL-8 production by inactivating NF-κB in endometriotic stromal cells.

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Abstract

ObjectiveTo investigate whether and how P, dienogest (synthetic progestin), and danazol affected tumor necrosis factor alpha (TNFalpha)-induced interleukin-8 (IL-8) expression in endometriotic stromal cells.DesignProspective study.SettingDepartment of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan.Patient(s)Ten patients who underwent laparoscopic surgery.Intervention(s)Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary.Main outcome measure(s)In the presence of TNFalpha (0.1 ng/mL) and E2 (10(-7) mol/L), the cells were cultured in medium with P (10(-6) mol/L), danazol (10(-6) mol/L), or dienogest (10(-7) mol/L). The expression of the IL-8 gene and protein was determined by Northern blotting and ELISA, respectively. Activation of nuclear factor (NF)-kappaB was evaluated by electrophoretic mobility shift assay.Result(s)Adding TNFalpha (0.1 ng/mL) together with E2 markedly enhanced gene and protein expression of IL-8. The up-regulation of the IL-8 gene and protein expression by TNFalpha and E2 was significantly reduced by the addition of P, dienogest, or danazol. Electrophoretic mobility shift assay revealed that incubation with TNFalpha and E2 induced NF-kappaB activation. Adding P, dienogest, or danazol attenuated NF-kappaB activation.Conclusion(s)The present study demonstrates for the first time that P and progestational compounds attenuate the expression of IL-8 by reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis.

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MeSH descriptors

Endometrium Interleukin-8 NF-kappa B Progesterone Progestins Tumor Necrosis Factor-alpha Endometrium Endometrium Endometrium Female Humans Interleukin-8 Interleukin-8 NF-kappa B NF-kappa B Progesterone Progestins Prospective Studies Stromal Cells Stromal Cells

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