TLR3 and TLR4 expression in healthy and diseased human endometrium.
BACKGROUND
Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases.


METHODS
TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3). The expression studies applied quantitative RT-PCR and immunolabelling of both proteins.


RESULTS
TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3).


CONCLUSIONS
Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.
Allhorn
Svenja
S
Institute of Anatomy II, University of Duisburg-Essen, Essen, Germany.
Böing
Carsten
C
Koch
Andrea A
AA
Kimmig
Rainer
R
Gashaw
Isabella
I
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D016889:Endometrial Neoplasms / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D017698:Postmenopause; D012333:RNA, Messenger / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D014591:Uterine Diseases / Q000378:metabolism*
D012333:RNA, Messenger; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4
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