Dienogest inhibits Toll-like receptor 4 expression induced by costimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells

Shizuka Mita; Yutaka Shimizu; Tatsuto Notsu; Kazunori Imada; Satoru Kyo

doi:10.1016/j.fertnstert.2011.09.040

Dienogest inhibits Toll-like receptor 4 expression induced by costimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells

Shizuka Mita, Yutaka Shimizu, Tatsuto Notsu, Kazunori Imada, Satoru Kyo

In: Fertility and Sterility · 2011 · vol. 96(6) , pp. 1485–1489.e4 · doi:10.1016/j.fertnstert.2011.09.040 · PMID:22014880 · W2088497719

article OA: closed CC0 ⤵ 19 in-corpus citations

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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Dienogest was found to inhibit the expression of Toll-like receptor 4, which was induced by the combined stimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells.

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Abstract

ObjectiveTo investigate the effect of dienogest on the expression of Toll-like receptor (TLR) 4 in human endometrial epithelial cells.DesignProspective basic research study.SettingPharmaceutical research center.Patient(s)None.Intervention(s)Not applicable.Main outcome measure(s)TLR4 in the immortalized progesterone receptor-expressing human endometrial epithelial cell line, EM-PR, was activated with lipopolysaccharide and high-mobility group box 1 (LPS/HMGB1) in the presence or absence of the synthetic progestin dienogest or endogenous progesterone. The production of interleukin (IL)-8, IL-6, and monocyte chemoattractant protein (MCP)-1 and the mRNA expression of TLR4 were measured with the use of ELISA and real-time reverse-transcription polymerase chain reaction respectively and nuclear factor (NF)-κB reporter gene assays were performed. The role of TLR4 was assayed with the use of TLR4-siRNA-transfected cells.Result(s)Coadministration of LPS/HMGB1 induced the production of IL-8, IL-6, and MCP-1, TLR4 mRNA expression, and NF-κB activity in EM-PR cells, and dienogest inhibited all of these parameters. TLR4 knockdown using TLR4 siRNA reduced IL-8 production.Conclusion(s)Dienogest inhibits TLR4 mRNA expression and subsequent IL-8 production induced by TLR4 agonists via an inhibitory effect on NF-κB activation in human endometrial epithelial cells. This pharmacologic effect of dienogest may contribute to its therapeutic effect on abnormal inflammation of endometrium.

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Dienogest via openalex
Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system via openalex
Dienogest, a synthetic progestin, inhibits the proliferation of immortalized human endometrial epithelial cells with suppression of cyclin D1 gene expression via openalex
Dienogest inhibits BrdU uptake with G0/G1 arrest in cultured endometriotic stromal cells via openalex
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Cited by (20)

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[1] Dienogest via openalex

[2] Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system via openalex

[3] Dienogest, a synthetic progestin, inhibits the proliferation of immortalized human endometrial epithelial cells with suppression of cyclin D1 gene expression via openalex

[4] Dienogest inhibits BrdU uptake with G0/G1 arrest in cultured endometriotic stromal cells via openalex

[5] Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis—a randomized, double-blind, multicenter, controlled trial via openalex

[6] Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis via openalex

[7] Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis via openalex

[8] Estrogen Receptor-β, Estrogen Receptor-α, and Progesterone Resistance in Endometriosis via openalex

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

[10] TLR3 and TLR4 expression in healthy and diseased human endometrium via openalex

[11] Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70 via openalex

[12] doi:10.4049/jimmunol.0900390 via openalex

[13] doi:10.1111/j.1447-0578.2007.00189.x via openalex

[14] doi:10.1016/j.cellbi.2007.01.034 via openalex

[15] doi:10.1089/vim.2010.0080 via openalex

[16] doi:10.1093/humrep/dep469 via openalex

[17] doi:10.1210/jc.2004-0241 via openalex

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[22] doi:10.1016/j.biocel.2009.10.009 via openalex

[23] doi:10.1152/ajpcell.00401.2005 via openalex

[24] doi:10.1016/j.smim.2006.12.002 via openalex

[25] doi:10.1016/j.imlet.2009.07.003 via openalex

[26] doi:10.1002/art.10540 via openalex

[27] doi:10.1016/j.molmed.2007.09.002 via openalex

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