LPS/TLR4-mediated stromal cells acquire an invasive phenotype and are implicated in the pathogenesis of adenomyosis

Abstract

The present study tested whether the LPS/TLR4 signal pathway in endometrial stromal cells is essential for the pathogenesis of adenomyosis. We tested the expression of TLR4, MD2 in the endometrium without adenomyosis (CE), the eutopic endometrium with adenomyosis (EuE) and the ectopic endometrium with adenomyosis (EE). We isolated the stromal cells from CE, EuE and EE (CESC, EuESC, EESC), treated with lipopolysaccharide (LPS) and TLR4 antagonist and detected the cell viability. And we also measured the key protein of the TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells. We found that the viability of experimental cells treated with LPS was significantly greater than that of the non-treated cells, blocked by the TLR4 antagonist VIPER. TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells stimulated by LPS, and it was inhibited by VIPER. This study suggested that stromal cells were activated by the TLR4 signalling pathway, which processed the cellular inflammatory proliferation and invasive growth involved in the pathogenesis of adenomyosis.

Berberine inhibits the LPS‑induced proliferation and inflammatory response of stromal cells of adenomyosis tissues mediated by the LPS/TLR4 signaling pathway

“…Emerging evidence suggested that this disease may be linked to the expression of inflammatory mediators and the induction of an immune response (4)(5)(6). A previous study by our group has confirmed that lipopolysaccharide (LPS) stimulates inflammatory cell proliferation and invasive growth of stromal cells in adenomyosis by activation of the Toll-like receptor (TLR4)/myeloid differentiation primary response gene 88/nuclear factor (NF)-κB signaling pathway, indicating that LPS/TLR4 signaling is implicated in the pathogenesis of adenomyosis (7). This provided a novel therapeutic strategy for adenomyosis via targeting TLR4 signaling.…”

“…The improper inflammatory response induced by LPS/TLR4 signaling has the potential to cause inflammatory disorders (24,25). Various studies have indicated that local and chronic inflammatory reactions in the uterus and peritoneal environment are likely to be associated with the pathogenesis of endometriosis/adenomyosis (7,26,27). Azuma et al (26) reported that LPS promoted the development of endometriosis through the NF-κB pathway in a murine model.…”

“…Indeed, numerous cytokines have been demonstrated to have a major role in the pathogenesis of adenomyosis (7,21,31,32). The present study focused on IL-6, IL-8, TGF-β, EGF, VEGF and MMP2 to investigate whether BBR inhibited the invasion, inflammatory response and maintenance of LPS-induced stromal cells from adenomyosis tissues.…”

“…Azuma et al (26) reported that LPS promoted the development of endometriosis through the NF-κB pathway in a murine model. A previous study by our group demonstrated that LPS/TLR4-mediated stromal cells acquire an invasive phenotype and are implicated in the pathogenesis of adenomyosis, which shed light on the mechanism underlying adenomyosis and provided a novel potential strategy for the clinical treatment of the disease (7).…”

LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia

“…Stimulation by lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, can lead to local infections or inflammatory processes through the Toll-like receptor 4 (TLR4)-mediated signalling pathway89. TLR4, a receptor for LPS, is one of the strongest inducers of inflammation10.…”