Progesterone and progestational compounds attenuate tumor necrosis factor alpha–induced interleukin-8 production via nuclear factor kappaB inactivation in endometriotic stromal cells
Open accessAbstract
Objective To 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.Design Prospective study.Setting Department 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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Dienogest and other progestins have putative mechanisms of action in endometriosis, including reduced growth, proliferation and neoangiogenesis of lesions and an antiinflammatory effect.
“Dienogest and other progestins have a number of putative mechanisms of action in endometriosis, including reduced growth, proliferation and neoangiogenesis of lesions [20, 21] as well as an antiinflammatory effect [22].”
From Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment (2012) · cites this paper as [22]
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- Authors
- Horie, S., Harada, T., Mitsunari, M., Taniguchi, F., Iwabe, T., & Terakawa, N.
- Affiliations
- Tottori University (JP)
- Corresponding author
- Harada, Tasuku
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 83
- Issue
- 5
- Pages
- 1530-1535
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2035455398
- Cited by
- 146
- References
- 22
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 13 · 2022: 6 · 2021: 14 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 5
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (13671715, 14370534)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- progesterone, dienogest, danazol, endometriosis, endometriotic stromal cells, TNF-α, interleukin-8, NF-κB activation, estradiol, hormone therapy
- MeSH terms
- Endometrium, Female, Humans, Progestins, Progesterone, Prospective Studies, Tumor Necrosis Factor-alpha, Interleukin-8, NF-kappa B, Stromal Cells
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