Abstract
Toll-like receptor (TLR) signal transduction is a central component of the primary innate immune response to pathogenic challenge. TLR4, a member of the TLR family, is highly expressed in the endometrial cells of the uterus and could thus be a key link between human chronic endometritis (CE) and the immune system. However, the exact biological function of TLR4 in human CE remains largely unexplored. The present study aimed to examine the role of TLR4 in human CE. A comprehensive expression and activation analysis of TLR4 in the endometrial cells of the uterus from patients with human CE (n=25) and normal endometrial (NE) tissue (n=15) was performed. Western blot analyses demonstrated that compared with NE, the protein expression TLR4 markedly increased in human CE. Endometrial tissue scrapings were also used for total RNA extraction and were transcribed and amplified by reverse transcription quantitative polymerase chain reaction. The results showed that significant upregulation of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and downregulation of IL-10 mRNA was observed in CE compared with the NE group. Furthermore, the protein of the signaling adapter myeloid differentiation factor-88 and the accessory molecules (TNF receptor associated factor 6 and transforming growth factor-β-activated kinase 1) were also detected in all the assayed tissues. Of note, differential expression (CE versus NE) was observed by immunoblotting at each level of the nuclear factor-κB signaling cascade, including inhibitor κBα and P65 (all P<0.05). The altered TLR4 and its corresponding downstream signaling molecules in CE cells may be of relevance for the progression of the human CE. These findings indicate that the evaluation of expression patterns of TLR4 holds promise for the treatment of human CE.
Highlights
Microbial disease of the female genital tract is common and of significant economic importance in humans
The Reverse transcription quantitative polymerase chain reac‐ tion (RT‐qPCR) and western blot analysis assays showed that the mRNA and protein expression levels of TLR4 were significantly increased in human chronic endometritis (CE) (n=7) compared with normal endometrial (NE) (n=5) (Fig. 1)
It was found that the expression of myeloid differentiation factor‐88 (MyD88), TRAF6 and transforming growth factor‐β‐activated kinase 1 (TAK1) molecules are involved in the mechanism of TLR4 in human endometrial endothelial cell responses to bacterial infection
Summary
Microbial disease of the female genital tract is common and of significant economic importance in humans. Microbial infections of the genital tract often infect the endometrium of humans to cause endometritis, uterine disease and infertility [1,2]. A number of the mechanisms underlying the recognition of microbial pathogens by the innate immune system in vertebrates have been identified during the past 15 years [3,4]. These mechanisms of innate immunity are important for classic immune cells, including neutrophils and macrophages, but are evident in the endometrial and ovarian cells of mammals.
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