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

Abstract：

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)-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.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

Mita S,Shimizu Y,Notsu T,Imada K,Kyo S

doi

10.1016/j.fertnstert.2011.09.040

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1485-1489.e4

issue

6

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(11)02615-X

journal_volume

96

pub_type

杂志文章

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