Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis.
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.
Department of Gynecology, Nanjing Municipal Organ Hospital, Nanjing, Jiangsu 210018, P.R. China.
Jinfen
J
Ju
Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
Liangpeng
L
Li
Department of Gynecology and Obstetrics, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
Jingyan
J
Xie
Department of Gynecology, Nanjing Municipal Organ Hospital, Nanjing, Jiangsu 210018, P.R. China.
Yan
Y
Wu
Department of Gynecology, Nanjing Municipal Organ Hospital, Nanjing, Jiangsu 210018, P.R. China.
Xi
X
Wu
Department of Gynecology, Nanjing Municipal Organ Hospital, Nanjing, Jiangsu 210018, P.R. China.
Weihon
W
Li
Toll-like receptor 4; chronic endometritis; inflammation; signaling pathway