interleukin-8 and dienogest

To investigate the effect of dienogest on the expression of Toll-like receptor (TLR) 4 in human endometrial epithelial cells.. Prospective basic research study.. Pharmaceutical research center.. None.. Not applicable.. 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.. 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.. 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.

Topics: Cells, Cultured; Dose-Response Relationship, Drug; Down-Regulation; Drug Evaluation, Preclinical; Endometrium; Epithelial Cells; Female; Gene Expression Regulation; Gene Knockdown Techniques; HMGB1 Protein; Hormone Antagonists; Humans; Interleukin-8; Lipopolysaccharides; Nandrolone; RNA, Small Interfering; Toll-Like Receptor 4