[34-36] The expression of TLR4 mRNA and protein was detected in Mφ, endometrial epithelial cells and stromal cells.[10, 31, 32] Reverse transcription polymerase chain reaction analysis also demonstrated the expression of CD14, MD2 and MyD88 mRNA in both endometrial epithelial cells (EEC) and endometrial stromal cells (ESC).[32] The expression levels of TLR4, CD14 and MD2 appeared Galunisertib mouse to be

higher in ESC compared with those in EEC. However, the expression levels of MyD88 were similar between ESC and EEC. Treatment of endometrial stromal cells with LPS significantly increased the production of a number of macromolecules, such as hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), IL-6, IL-8 and tumor necrosis factor (TNF)-α in a dose-dependent fashion.[32, 37, 38] A

significantly more growth-promoting effect of LPS was observed on endometrial cells derived from women with endometriosis when compared with similar cells derived from control women.[37, 38] The stimulatory effect of LPS was inhibited by the addition of neutralizing antibodies for TLR4 and also by an LPS antagonist, polymyxin B.[10] This indicates that Mφ, ESC and EEC express TLR4 and respond to LPS through TLR4. In fact, we recently demonstrated that both ESC and EEC were able to significantly proliferate in response to LPS and this growth-promoting effect of LPS

was abrogated after pretreatment of cells with anti-TLR4 antibody.[8, 10, 39] Because there are other Panobinostat molecular weight exogenous and endogenous ligands for TLR4 Digestive enzyme in addition to LPS, we presume that blocking of TLR4 alone is more effective in order to suppress inflammatory response in the pelvic environment and cell growth. A recent study[32] demonstrated that LPS was able to stimulate TLR4- and CD14-mediated increased production of IL-8 by ESC. This effect of LPS was associated with the activation of NF-κB as examined by nuclear translocation of NF-κB in ESC. On the other hand, LPS alone did not stimulate IL-8 secretion in EEC. However, LPS did stimulate IL-8 secretion from EEC in the presence of soluble CD14. These findings indicate that the TLR4 system may represent local immunity in the human endometrium with different modes of TLR4 actions between ESC and EEC. We presume that an innate immune system and ovarian steroid hormones may participate either alone or in an orchestrated fashion in the growth regulation of endometriosis. The different macromolecules as secreted by Mφ in the pelvic environment are believed to enhance the growth of endometriosis. However, the initial inflammatory mediator that stimulates Mφ for the production of different cytokines and growth factors was poorly described.