TAK1 activation for cytokine synthesis and proliferation of endometriotic cells

Abstract Endometriosis causes pelvic pain and infertility in women of reproductive age. We explored TNFα-induced specific signaling pathways and gene expressions in endometriotic stromal cells (ESCs). Based on the data of the pathway specific cDNA array, we analyzed the role of TAK1, which is believed to work as a common mediator for NF-κB and MAPK pathways. Using the NF-κB pathway array, we found that TNFα upregulated ICAM-3, IL-6, IL-8, TAK1, JNK2, RelA, and TLR4 expressions. TNFα augmented the phosphorylation of TAK1. By transfection of TAK1 siRNA, TNFα-induced phosphorylation of IκBα, JNK1/2, and p38MAPK, as well as IL-6 or IL-8 expression, were repressed. TAK1 silencing in TNFα-pretreated ESCs caused a decrease in the proportion of cells in S-phase, and reduced TNFα-promoted BrdU incorporation. We provide the first evidence that TNFα and its downstream TAK1, which are key mediators for NF-κB and MAPK pathways, may be involved in the pathogenesis of endometriosis.