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

Oleh:

Mita, Shizuka ; Shimizu, Yutaka ; Notsu, Tatsuto ; Imada, Kazunori

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 96 no. 06 (Dec. 2011), page 1485-1489.
Topik: Dienogest; Toll-like receptor 4; endometrial epithelial cells; inflammation; nuclear factor-?B

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2011.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Objective To investigate the effect of dienogest on the expression of Toll-like receptor (TLR) 4 in human endometrial epithelial cells. Design Prospective basic research study. Setting Pharmaceutical 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)-?B 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-?B 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-?B 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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