Abstract
BackgroundToll-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.MethodsTLR3 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.ResultsTLR3 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).ConclusionOur data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.
Highlights
Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens
In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls
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
Summary
Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens. Reproductive Biology and Endocrinology 2008, 6:40 http://www.rbej.com/content/6/1/40 response gene 88 (MyD88), myelin and lymphocyte protein Mal, translocation associated membrane protein (TRAM) and sterile alpha and TIR motif containing (SARM), TLRs activate signalling pathways of mitogenactivated protein kinases, nuclear factor kappa-B (NFêB), signal transducers and activators of transcription (STATs) or the activator protein 1 (AP1) [1,2,3]. These signalling cascades result in enhanced secretion of various pro- and anti-inflammatory cytokines such as interferons, tumor necrosis factor α (TNFα) and interleukins IL4, IL8, and IL12 [1,2]. Recent studies have determined the expression pattern of TLR3 [4,9,10,11,12] and TLR4 [4,10,11,12,13,14] in the human endometrium, but their possible involvement in the pathogenesis of endometrial diseases associated with inflammation remains to be elucidated
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